Nanomaterials for Cancer PhototheranosticsView this Special Issue
Review Article | Open Access
Advances on the Use of Biodegradable Proteins/Peptides in Photothermal Theranostics
Recently, photothermal therapy (PTT) which employs light-induced heating to destroy cancer tissues/cells has received tremendous attention due to its improved selectivity and minimal invasion to surrounding healthy tissues. A variety of photothermal conversion agents (PTCAs) with high near-infrared (NIR) light absorbance have been widely explored for NIR light-induced PTT. However, many of them cannot be used directly in vivo owing to their nonbiodegradability, immunogenicity, poor pharmacokinetics, or potential long-term toxicity. Proteins and peptides with inherent biocompatibility and biodegradability have been used as delivery vehicles for PTCAs or used as biotemplates to direct the synthesis of PTCAs. In this review, we will summarize recent advances in the development of protein/peptide-based photothermal cancer theranostics. The perspectives and challenges of these nanoplatforms will also be discussed.
Photothermal therapy (PTT), which employs light-induced heating to destroy cancer tissues/cells, is a new promising strategy to treat cancer due to its improved selectivity and minimal invasion to surrounding healthy tissues . In general, PTT involves noninvasive light and photothermal conversion agents (PTCAs) that show low toxicity in dark and therapeutic effect under light irradiation. So the PTT can achieve superimposed targeting effect: on the one hand, the photoabsorbing agent can be designed to nanosized and ligand-modified particle so as to target cancer via passive and active targeting; on the other hand, the light can be applied only in cancer site to reduce side effect. Particularly, near-infrared (NIR) light (650–950 nm) induced PTT holds much promise because of the relatively low absorption/scattering of skin, tissue, blood, and water in the NIR region . In the NIR light-induced PTT, PTCAs are crucial elements that absorb NIR light energy and convert it into heat and thus raise the local temperature of tumor to kill them. In the past decades, a variety of inorganic/organic nanomaterials, such as noble metal nanomaterials (Au, Ag, and Pt) [3–7], carbon-based nanomaterials (graphene oxide and carbon nanotube) [8–10], semiconductor nanomaterials (WS2, CuS, and Se) [11–16], and NIR dyes (indocyanine green, cypate, IR780, and IR825) [17–19], as well as semiconducting polymer nanomaterials (polyaniline and polypyrrole) [20–22], have been widely explored as PTCAs for PTT. These PTCAs exhibit high NIR absorbance; however, many of them cannot be used directly in vivo owing to nonbiodegradability, immunogenicity, poor pharmacokinetics, or potential long-term toxicity. Therefore, development of novel photothermal nanosystems is highly desirable to accelerate the clinical translation of PTT.
In the past few years, proteins and peptides have been developed as excellent delivery materials for many diagnostic/therapeutic agents due to their inherent biocompatibility and biodegradability [23–25] (Figure 1). On the one hand, proteins/peptides can encapsulate hydrophobic nanoparticles or molecules through hydrophobic interactions and thus improve the biocompatibility and water solubility of the nanoagents [26–28]. On the other hand, proteins/peptides can be used as biotemplates to synthesize nanoparticles directly [29–33]. Meanwhile, proteins/peptides contain a large number of functional groups (i.e., carboxylic and amino groups) that can easily conjugate functional substances, such as drugs, NIR dyes, photosensitizers, targeting ligands, and imaging agents, to achieve “All-in-One” multifunctional theranostics .
Considering the unique properties of proteins/peptides, recently, various protein-based photothermal nanoplatforms, which can combine the advantages and functionalities of both proteins/peptides and PTCAs, have been developed for PTT (Table 1). Herein, we will give a brief review on recent advances in the development of protein-based photothermal cancer theranostics. The perspectives and challenges of these nanoplatforms will also be discussed.
2. Serum Albumin-Based Photothermal Theranostics
Serum albumin, the major component of serum proteins, is an attractive biomacromolecule with the merits of biodegradability, nontoxicity, nonimmunogenicity, and easily biological production and purification . Among the available serum albumin, human serum albumin (HSA) and bovine serum albumin (BSA) are two of the most used proteins.
HSA, which contains 585 amino acid residues with a relative molecular weight of 66.5 KDa, is the most abundant protein in human plasma (~42 g/L) and plays an important role in transporting fatty acids, amino acids, steroids, and metal ions . It is an endogenous protein, which has been approved by the US Food and Drug Administration (FDA) for intravenous administration. Furthermore, some studies showed that HSA coated nanoparticles possess active tumor-targeting abilities via gp60 and SPARC receptor-mediated transcytosis .
Recently, numerous studies have reported HSA-based photothermal nanosystems for PTT. For example, Sheng et al. reported a kind of smart nanoparticle based on HSA and indocyanine green (ICG) for dual-modal imaging-guided synergistic phototherapy . ICG is a FDA-approved multifunctional NIR dye which can be used not only for NIR fluorescence (FL) imaging and photoacoustic (PA) imaging but also for PTT and photodynamic therapy (PDT). In this work, the disulfide bonds of HSA were firstly cleaved by adding excessive reducing agent to obtain free sulfhydryl groups. Then the reduced HSA can reassemble into HSA nanoparticles through the formation of intermolecular disulfide bonds. During this reassembling process, the ICG molecules were loaded into HSA nanoparticles. Thus the final HSA-ICG nanoparticles are composed of HSA and ICG without any other toxic chemicals, which show excellent biosafety. In vivo dual-modal imaging could clearly differentiate tumor tissue with normal tissue and thus precisely guide PTT/PDT cancer treatment. In a more recent work, Chen and coworkers reported a nanodrug that obtained via self-assembly of HSA, ICG, and paclitaxel (PTX, an effective antitumor drug) at a predetermined molar ratio (Figure 2(a)) . The structure of this nanodrug is similar to a FDA-approved formulation (trade name: Abraxane), which takes advantages of imaging-guided PTT and chemotherapy. Both HSA-ICG nanoparticle and HSA-ICG-PTX nanodrug are composed of FDA-approved components and demonstrated great antitumor performance which may be promising photothermal theranostics for clinical applications.
HSA has also been exploited as a nanocarrier for other NIR dyes, such as IR825 and IR780 [39–41]. These nanosystems also showed high antitumor effects in animal experiments. Rong et al. designed a NIR cyanine dye by introducing a rigid cyclohexenyl ring to the heptamethine chain to obtain a heptamethine dye CySCOOH with higher fluorescence quantum yield and greater stability than ICG . By covalent conjugation of CySCOOH onto HSA (Figure 2(b)), the as-prepared HSA@CySCOOH nanoplatform is highly efficient for multimodality imaging-guided PTT. Compared with dye-encapsulated HSA-based photothermal theranostics, the obtained HSA@CySCOOH conjugates showed several advantages such as good stability without the risk of dye leakage in the blood circulation and high dye loading efficiency.
HSA contains a variety of hydrophilic and hydrophobic amino acids and a large number of functional groups, so it also can be used to modify inorganic nanoparticles by hydrophobic interactions or cross-link. Topete et al. reported a multifunctional nanotheranostic platform, which is composed of PLGA/doxorubicin (DOX)-core Au-branched shell nanostructure (BGNSHs) and HSA/ICG/folic acid complex (HSA-ICG-FA) surface coating . The nanotheranostic platform would achieve multifunctional abilities, such as PTT provided by the gold nanolayer, fluorescence imaging and PDT provided by the ICG, chemotherapy provided by the DOX, and active targeting provided by the FA. Peralta et al. employed a desolvation and cross-linking approach to develop gold nanorods (Au NRs)-PTX-loaded HSA nanoparticles . As shown in Figure 2(c), the PTCAs (Au NRs) and antitumor drug (PTX) were encapsulated into the HSA nanoparticles simultaneously. The resulting Au NR-PTX-HSA nanoparticles demonstrated great antitumor effect of combination therapy.
BSA, which derived from cows, is also a widely used carrier for cancer theranostics due to its abundance and low cost. BSA can sequester inorganic ions through a simulative biomineralization process, which trigger the formation of nanoclusters in mild conditions . In a recent work, Wang et al. developed smart cypate-grafted gadolinium oxide nanocrystals (Cy-GdNCs) . BSA-based biomineralization approach was employed to synthesize GdNCs, followed by the covalent conjugation of Cy to BSA. This Cy-GdNC can achieve tumor-targeting trimodal FL/PA/magnetic resonance (MR) imaging and pH-responsive PTT, resulting in effective tumor ablation. BSA also can be used as the biotemplate to synthesize inorganic PTCAs. For example, Zhang et al. synthesized copper sulfide (CuS) nanoparticles using BSA as a template . This method has several benefits such as high efficiency and mild synthesis condition. In vitro and in vivo results showed that the BSA-CuS nanoparticles had excellent biocompatibility and efficient PTT effect. In addition, BSA can be used as a reductant and stabilizer for the synthesis of PTCAs. Sheng et al. developed a facile fabrication method of nanoscale reduced graphene oxide (nano-rGO) . BSA, as a reductant and coating material, can reduce nano-GO to nano-rGO with high NIR absorption, high stability, and low cytotoxicity. The BSA-based nano-rGO showed excellent performance for in vivo PA imaging and PTT.
BSA is also a kind of commonly used vehicle for organic PTCAs (NIR dyes, polymeric nanoparticles, etc.) delivery. For example, the squaraine, IR825, or polypyrrole loaded BSA nanoplatforms were developed for imaging-guided therapy [28, 49, 50]. The in vivo results evidenced the feasibility of using those nanoplatforms as photothermal theranostics for multimodality imaging and phototherapy.
3. Other Proteins-Based Photothermal Theranostics
Besides serum albumin, several other proteins with special molecular structures or functions, such as ferritin, hepatitis B virus (HBV) core protein, gelatin, antibodies, and phycocyanin (PC), have been used as building blocks for the construction of protein-based photothermal theranostics.
Ferritin, a protein of 450 kDa consisting of 24 subunits, has a nanocage structure with external and internal diameters of 12 and 8 nm, respectively. Ferritin serves to store iron in a nontoxic form, to deposit it in a safe form, and to transport it to areas where it is required. Because of the cage-like structure, ferritin has also been successfully used as nanocarrier of therapeutic agent or biotemplate for the fabrication of nanoparticles [23, 24]. The internal cavity allows high loading efficiency of therapeutic agents and the protein shells as a coating to prevent coagulation/aggregation between nanoparticles.
Recently, Huang et al. reported a novel theranostic platform based on IR820 (NIR dye)-loaded ferritin nanocages with strong absorbance in the NIR region . IR820 molecules were loaded into the internal cavity by “opening” and “closing” the ferritin nanocages. Under 550 nm light irradiation, the theranostic platform can achieve FL imaging with high fluorescence quantum yield, while under 808 nm NIR light irradiation, the theranostic platform can achieve PA imaging and PTT with high photothermal conversion efficiency. In vivo results showed that 100% tumor elimination was achieved by intravenous injection of IR820-loaded ferritin nanocages, under a low laser power density of 0.5 W/cm2. In another work, Wang et al. reported biomineralization-inspired synthesis and photothermal application of CuS/-ferritin nanocages . As shown in Figure 3(a), Cu and ions were firstly encapsulated into the ferritin cages. After the addition of S ions, CuS/-Fn nanocages were obtained. The in vitro (Figure 3(b)) and in vivo (Figures 3(c)–3(e)) results indicated that the CuS-Fn nanocages achieved superior tumor therapeutic efficiency without systemic toxicity.
3.2. HBV Core Protein
Protein-based particles that are self-assembled inside cells have been developed for a variety of bioassays and biomedical applications . For example, when expressed in Escherichia coli, the HBV core protein forms a core shell capsid with a diameter of 36 nm. Based on the core shell capsid, Kwon et al. developed a protein/gold core/shell nanoparticle (PGCS-NP) that can be used as a PTCA for targeted cancer therapy without in vivo toxicity (Figure 4) . Hexahistidine (H6), biotinylated peptide (BP), hexatyrosine (Y6), and affibody peptides for human epidermal growth factor receptor I (EGFR) were used to modify the HBV core protein. Then the modified HBV core proteins were self-assembled into the engineered particles, and gold ions are reduced to gold dots (1–3 nm) by the reduction potential of Y6 residues. The resulted nanoplatform has uniform particle size distribution, high colloidal stability, and excellent photothermal activity. Most importantly, as the nanoplatform was disassembled with time, the small gold dots were released and rapidly excreted from liver and kidney, indicating that the nanoplatform can be used as safe PTCAs without concern of long-term toxicity.
Gelatin, an irreversibly hydrolyzed form of collagen, is a mixture of proteins and peptides obtained from the skin, bones, and connective tissues of various animals. Gelatin has many excellent properties such as easy functionalization and good biocompatibility and can be effectively digested by gelatinase into nontoxic peptides. Zha et al. developed multifunctional CuS nanoparticles stabilized with DOX-conjugated gelatin (CuS@Gel-DOX) . In this case, CuS nanoparticle was used as the PTCA and PA contrast agent; DOX was used as a model antitumor drug. Thus the as-prepared CuS@Gel-DOX nanosystem can achieve simultaneous PA imaging, PTT, and enzyme-responsive drug release. Lin et al. developed nanocomposites that incorporated Cu9S5@mSiO2 nanoparticles or polyaniline nanoparticles into poly(-caprolactone) and gelatin [55, 56]. The as-prepared nanocomposites were surgically implanted into tumors in mice and followed by efficient PTT treatment.
Antibody, also known as immunoglobulin, is a kind of large, Y-shape protein produced by plasma cells that is used by the immune system to identify and neutralize pathogens. In recent years, some antibodies (anti-EGFR) were also used as tumor-targeting ligands, since the EGFR is overexpressed in many malignant cells. Yu et al. reported a kind of anti-EGFR-coated ICG-loaded polymer/salt nanocapsule for in vitro PTT . The results indicated that the anti-EGFR-coated nanocapsules had significant thermal toxicity upon 808 nm NIR light irradiation. In another work, Zhang et al. developed the EGFR monoclonal antibody (mAb) modified AuNRs (EGFRmAb-AuNR) for targeted PTT on Hep-2 cells .
PC, a pigment-protein complex from the light-harvesting phycobiliprotein family, is a water-soluble protein and is frequently used as a coloring agent in food and cosmetics. It also can be used as a photosensitizer for generating reactive oxygen species (ROS) under excitation of appropriate light . Recently, Liao and Zhang developed a multiwalled carbon nanotube-chitosan-PC complex (MWNT-CS-PC) for PTT and PDT . Both CS and PC improve the water solubility and stability of MWNTs. Additionally, PC is a photosensitizer that is able to generate cytotoxic ROS for PDT, and MWNT is a PTCA that is able to generate heat for PTT.
4. Peptides-Based Photothermal Theranostics
Peptides are short chains of amino acid monomers linked by peptide bonds. Proteins are composed of one or more peptides arranged in a biologically functional way. The boundaries that distinguish peptides from proteins are not absolute: long peptides such as amyloid beta have been referred to as proteins, and smaller proteins like insulin have been considered peptides. Like proteins, peptides were also employed as building blocks for the development of photothermal theranostics. Huang et al. developed an endogenous alkaline phosphatase- (ALP-) triggered coassembly strategy to form tumor-specific nanofibers, which based on ICG and NapFFKYp (an ALP-responsive peptide), for FL/PA dual-modality imaging-guided PTT (Figure 5) . The ICG-doped nanofiber showed significantly enhanced NIR absorbance and unique PA and PTT properties. Synthetic polypeptides are also promising nanocarriers of PTCAs because they own similar component and structure to natural proteins. For example, Yang et al. reported an ICG and cypate-loaded poly(L-aspartic acid)-based micelle system with multiple advantages for FL imaging and PTT . These micelles exhibit high loading capacity, good stability, enhanced cellular uptake efficiency, and efficient photothermal efficacy. Wu et al. reported ICG-loaded polymeric micelles, which self-assembled from amphiphilic poly(ethylene glycol)-b-poly(L-lysine)-b-poly(L-leucine) (PEG-PLL-PLLeu), for tumor imaging and PTT . Compared with free ICG, PEG-PLL-PLLeu-ICG micelles significantly improved the quantum yield and fluorescent stability of ICG. In vitro photothermal ablation studies also proved the feasibility of the PEG-PLL-PLLeu-ICG for tumor PTT.
5. Conclusion and Perspective
Natural proteins and synthetic peptides are playing important roles in cancer theranostics. A variety of protein-based theranostics have emerged in the past few years. The capabilities of proteins to load different PTCAs endow them with many advantages, such as improved water solubility and biocompatibility, prolonged blood circulation time, and multifunctional modification.
However, the clinical translation of protein-based photothermal theranostics is still facing many challenges. Firstly, as natural polymers, proteins are heterogeneous mixtures and exhibit batch-to-batch variation, which may hinder the industrial application of protein-based nanoplatforms . Secondly, although many photothermal nanoplatforms have demonstrated their high PTT efficacy in preclinical animal experiments, there are rarely FDA-approved proteins and PTCAs that are safe for use in humans. Thirdly, the poor photothermal stability of protein-organic agents and the potential long-term toxicity of protein-inorganic agents severely limit their future clinical applications. In addition, the PTCAs loading efficiency of most protein-based nanoplatforms are often too low, resulting in limited PTT efficacy.
Studies will continue to further improve the clinical applicability of protein-based photothermal theranostics. For example, the recombinant protein technology is a promising strategy to overcome the batch-to-batch variation of protein-based platforms. More and more protein-based photothermal theranostics with high photothermal stability, great long-term biosafety, and high tumor accumulation have been developed for PTT. Although the development of PTT is still at an early stage, protein-based photothermal theranostics may have great potential for clinical applications to treat cancer patients in the near future.
The authors declare that there are no competing interests regarding the publication of this paper.
This work was supported by the National Science Foundation of China (51573096 and 81401465).
- Q. Chen, H. Ke, Z. Dai, and Z. Liu, “Nanoscale theranostics for physical stimulus-responsive cancer therapies,” Biomaterials, vol. 73, pp. 214–230, 2015.
- V. Shanmugam, S. Selvakumar, and C.-S. Yeh, “Near-infrared light-responsive nanomaterials in cancer therapeutics,” Chemical Society Reviews, vol. 43, no. 17, pp. 6254–6287, 2014.
- P. Huang, J. Lin, W. Li et al., “Biodegradable gold nanovesicles with an ultrastrong plasmonic coupling effect for photoacoustic imaging and photothermal therapy,” Angewandte Chemie—International Edition, vol. 52, no. 52, pp. 13958–13964, 2013.
- T. Sun, Y. Wang, Y. Wang et al., “Using SV119-gold nanocage conjugates to eradicate cancer stem cells through a combination of photothermal and chemo therapies,” Advanced Healthcare Materials, vol. 3, no. 8, pp. 1283–1291, 2014.
- J. Song, X. Yang, O. Jacobson et al., “Sequential drug release and enhanced photothermal and photoacoustic effect of hybrid reduced graphene oxide-loaded ultrasmall gold nanorod vesicles for cancer therapy,” ACS Nano, vol. 9, no. 9, pp. 9199–9209, 2015.
- P. Huang, P. Rong, J. Lin et al., “Triphase interface synthesis of plasmonic gold bellflowers as near-infrared light mediated acoustic and thermal theranostics,” Journal of the American Chemical Society, vol. 136, no. 23, pp. 8307–8313, 2014.
- J. Lin, S. Wang, P. Huang et al., “Photosensitizer-loaded gold vesicles with strong plasmonic coupling effect for imaging-guided photothermal/photodynamic therapy,” ACS Nano, vol. 7, no. 6, pp. 5320–5329, 2013.
- L. Zhang, P. Rong, M. Chen, S. Gao, and L. Zhu, “A novel single walled carbon nanotube (SWCNT) functionalization agent facilitating in vivo combined chemo/thermo therapy,” Nanoscale, vol. 7, no. 39, pp. 16204–16213, 2015.
- J. Ge, Q. Jia, W. Liu et al., “Red-emissive carbon dots for fluorescent, photoacoustic, and thermal theranostics in living mice,” Advanced Materials, vol. 27, no. 28, pp. 4169–4177, 2015.
- Y. Wang, H. Wang, D. Liu, S. Song, X. Wang, and H. Zhang, “Graphene oxide covalently grafted upconversion nanoparticles for combined NIR mediated imaging and photothermal/photodynamic cancer therapy,” Biomaterials, vol. 34, no. 31, pp. 7715–7724, 2013.
- L. Cheng, J. Liu, X. Gu et al., “PEGylated WS2 nanosheets as a multifunctional theranostic agent for in vivo dual-modal CT/photoacoustic imaging guided photothermal therapy,” Advanced Materials, vol. 26, no. 12, pp. 1886–1893, 2014.
- M. Zhou, J. Li, S. Liang, A. K. Sood, D. Liang, and C. Li, “CuS nanodots with ultrahigh efficient renal clearance for positron emission tomography imaging and image-guided photothermal therapy,” ACS Nano, vol. 9, no. 7, pp. 7085–7096, 2015.
- J. Cui, R. Jiang, S. Y. Xu, G. F. Hu, and L. Y. Wang, “Cu7S4 nanosuperlattices with greatly enhanced photothermal efficiency,” Small, vol. 11, no. 33, pp. 4183–4190, 2015.
- C. M. Hessel, V. P. Pattani, M. Rasch et al., “Copper selenide nanocrystals for photothermal therapy,” Nano Letters, vol. 11, no. 6, pp. 2560–2566, 2011.
- W. Yin, L. Yan, J. Yu et al., “High-throughput synthesis of single-layer MoS2 nanosheets as a near-infrared photothermal-triggered drug delivery for effective cancer therapy,” ACS Nano, vol. 8, no. 7, pp. 6922–6933, 2014.
- L. Zhang, S. Gao, F. Zhang, K. Yang, Q. Ma, and L. Zhu, “Activatable hyaluronic acid nanoparticle as a theranostic agent for optical/photoacoustic image-guided photothermal therapy,” ACS Nano, vol. 8, no. 12, pp. 12250–12258, 2014.
- M. Zheng, C. Yue, Y. Ma et al., “Single-step assembly of DOX/ICG loaded lipid-polymer nanoparticles for highly effective chemo-photothermal combination therapy,” ACS Nano, vol. 7, no. 3, pp. 2056–2067, 2013.
- L. Cheng, W. He, H. Gong et al., “PEGylated micelle nanoparticles encapsulating a non‐fluorescent near‐infrared organic dye as a safe and highly‐effective photothermal agent for in vivo cancer therapy,” Advanced Functional Materials, vol. 23, no. 47, pp. 5893–5902, 2013.
- H. Gong, Z. Dong, Y. Liu et al., “Engineering of multifunctional nano‐micelles for combined photothermal and photodynamic therapy under the guidance of multimodal imaging,” Advanced Functional Materials, vol. 24, no. 41, pp. 6492–6502, 2014.
- J. Yang, J. Choi, D. Bang et al., “Convertible organic nanoparticles for near-infrared photothermal ablation of cancer cells,” Angewandte Chemie—International Edition, vol. 50, no. 2, pp. 441–444, 2011.
- Q. Tian, Q. Wang, K. X. Yao et al., “Multifunctional polypyrrole@Fe3O4 nanoparticles for dual-modal imaging and in vivo photothermal cancer therapy,” Small, vol. 10, no. 6, pp. 1063–1068, 2014.
- X. Liang, Y. Li, X. Li et al., “PEGylated polypyrrole nanoparticles conjugating gadolinium chelates for dual-modal MRI/photoacoustic imaging guided photothermal therapy of cancer,” Advanced Functional Materials, vol. 25, no. 9, pp. 1451–1462, 2015.
- Z. Zhen, W. Tang, H. Chen et al., “RGD-modified apoferritin nanoparticles for efficient drug delivery to tumors,” ACS Nano, vol. 7, no. 6, pp. 4830–4837, 2013.
- X. Lin, J. Xie, G. Niu et al., “Chimeric ferritin nanocages for multiple function loading and multimodal imaging,” Nano Letters, vol. 11, no. 2, pp. 814–819, 2011.
- A. O. Elzoghby, W. M. Samy, and N. A. Elgindy, “Protein-based nanocarriers as promising drug and gene delivery systems,” Journal of Controlled Release, vol. 161, no. 1, pp. 38–49, 2012.
- Z. Liu, N. Chen, C. Dong et al., “Facile construction of near infrared fluorescence nanoprobe with amphiphilic protein-polymer bioconjugate for targeted cell imaging,” ACS Applied Materials & Interfaces, vol. 7, no. 34, pp. 18997–19005, 2015.
- Z. Liu, C. Dong, X. Wang et al., “Self-assembled biodegradable protein-polymer vesicle as a tumor-targeted nanocarrier,” ACS Applied Materials & Interfaces, vol. 6, no. 4, pp. 2393–2400, 2014.
- Q. Chen, C. Wang, L. Cheng, W. He, Z. Cheng, and Z. Liu, “Protein modified upconversion nanoparticles for imaging-guided combined photothermal and photodynamic therapy,” Biomaterials, vol. 35, no. 9, pp. 2915–2923, 2014.
- J. Lin, Z. Zhou, Z. Li et al., “Biomimetic one-pot synthesis of gold nanoclusters/nanoparticles for targeted tumor cellular dual-modality imaging,” Nanoscale Research Letters, vol. 8, no. 1, pp. 2–7, 2013.
- P. Huang, L. Bao, D. Yang et al., “Protein-directed solution-phase green synthesis of BSA-conjugated M(x)Se(y) (M = Ag, Cd, Pb, Cu) nanomaterials,” Chemistry—An Asian Journal, vol. 6, no. 5, pp. 1156–1162, 2011.
- P. Huang, D.-P. Yang, C. Zhang et al., “Protein-directed one-pot synthesis of Ag microspheres with good biocompatibility and enhancement of radiation effects on gastric cancer cells,” Nanoscale, vol. 3, no. 9, pp. 3623–3626, 2011.
- P. Huang, Y. Kong, Z. Li, F. Gao, and D. Cui, “Copper selenide nanosnakes: bovine serum albumin-assisted room temperature controllable synthesis and characterization,” Nanoscale Research Letters, vol. 5, no. 6, pp. 949–956, 2010.
- P. Huang, Z. Li, H. Hu, and D. Cui, “Synthesis and characterization of bovine serum albumin-conjugated copper sulfide nanocomposites,” Journal of Nanomaterials, vol. 2010, Article ID 641545, 6 pages, 2010.
- S. Liu, M. Hassink, R. Selvaraj et al., “Efficient F-18 labeling of cysteine-containing peptides and proteins using tetrazine-trans-cyclooctene ligation,” Molecular Imaging, vol. 12, no. 2, pp. 121–128, 2013.
- A. O. Elzoghby, W. M. Samy, and N. A. Elgindy, “Albumin-based nanoparticles as potential controlled release drug delivery systems,” Journal of Controlled Release, vol. 157, no. 2, pp. 168–182, 2012.
- B. Elsadek and F. Kratz, “Impact of albumin on drug delivery—new applications on the horizon,” Journal of Controlled Release, vol. 157, no. 1, pp. 4–28, 2012.
- Z. Sheng, D. Hu, M. Zheng et al., “Smart human serum albumin-indocyanine green nanoparticles generated by programmed assembly for dual-modal imaging-guided cancer synergistic phototherapy,” ACS Nano, vol. 8, no. 12, pp. 12310–12322, 2014.
- Q. Chen, C. Liang, C. Wang, and Z. Liu, “An imagable and photothermal ‘abraxane-like’ nanodrug for combination cancer therapy to treat subcutaneous and metastatic breast tumors,” Advanced Materials, vol. 27, no. 5, pp. 903–910, 2015.
- Q. Chen, C. Wang, and Z. Zhan, “Near-infrared dye bound albumin with separated imaging and therapy wavelength channels for imaging-guided photothermal therapy,” Biomaterials, vol. 35, no. 28, pp. 8206–8214, 2014.
- Q. Chen, C. Liang, X. Wang, J. He, Y. Li, and Z. Liu, “An albumin-based theranostic nano-agent for dual-modal imaging guided photothermal therapy to inhibit lymphatic metastasis of cancer post surgery,” Biomaterials, vol. 35, no. 34, pp. 9355–9362, 2014.
- C. Jiang, H. Cheng, A. Yuan, X. Tang, J. Wu, and Y. Hu, “Hydrophobic IR780 encapsulated in biodegradable human serum albumin nanoparticles for photothermal and photodynamic therapy,” Acta Biomaterialia, vol. 14, pp. 61–69, 2015.
- P. Rong, P. Huang, Z. Liu et al., “Protein-based photothermal theranostics for imaging-guided cancer therapy,” Nanoscale, vol. 7, no. 39, pp. 16330–16336, 2015.
- A. Topete, M. Alatorre-Meda, P. Iglesias et al., “Fluorescent drug-loaded, polymeric-based, branched gold nanoshells for localized multimodal therapy and imaging of tumoral cells,” ACS Nano, vol. 8, no. 3, pp. 2725–2738, 2014.
- D. V. Peralta, Z. Heidari, S. Dash, and M. A. Tarr, “Hybrid paclitaxel and gold nanorod-loaded human serum albumin nanoparticles for simultaneous chemotherapeutic and photothermal therapy on 4T1 breast cancer cells,” ACS Applied Materials & Interfaces, vol. 7, no. 13, pp. 7101–7111, 2015.
- R. De La Rica and H. Matsui, “Applications of peptide and protein-based materials in bionanotechnology,” Chemical Society Reviews, vol. 39, no. 9, pp. 3499–3509, 2010.
- Y. Wang, T. Yang, H. Ke et al., “Smart albumin-biomineralized nanocomposites for multimodal imaging and photothermal tumor ablation,” Advanced Materials, vol. 27, no. 26, pp. 3874–3882, 2015.
- C. Zhang, Y. Fu, X. Zhang, C. Yu, Y. Zhao, and S. Sun, “BSA-directed synthesis of CuS nanoparticles as a biocompatible photothermal agent for tumor ablation in vivo,” Dalton Transactions, vol. 44, no. 29, pp. 13112–13118, 2015.
- Z. Sheng, L. Song, J. Zheng et al., “Protein-assisted fabrication of nano-reduced graphene oxide for combined in vivo photoacoustic imaging and photothermal therapy,” Biomaterials, vol. 34, no. 21, pp. 5236–5243, 2013.
- F.-P. Gao, Y.-X. Lin, L.-L. Li et al., “Supramolecular adducts of squaraine and protein for noninvasive tumor imaging and photothermal therapy in vivo,” Biomaterials, vol. 35, no. 3, pp. 1004–1014, 2014.
- X. Song, C. Liang, H. Gong, Q. Chen, C. Wang, and Z. Liu, “Photosensitizer-conjugated albumin-polypyrrole nanoparticles for imaging-guided in vivo photodynamic/photothermal therapy,” Small, vol. 11, no. 32, pp. 3932–3941, 2015.
- P. Huang, P. Rong, A. Jin et al., “Dye-loaded ferritin nanocages for multimodal imaging and photothermal therapy,” Advanced Materials, vol. 26, no. 37, pp. 6401–6408, 2014.
- Z. Wang, P. Huang, O. Jacobson et al., “Biomineralization-inspired synthesis of copper sulfide-ferritin nanocages as cancer theranostics,” ACS Nano, vol. 10, no. 3, pp. 3453–3460, 2016.
- K. C. Kwon, J. H. Ryu, J.-H. Lee et al., “Proteinticle/gold core/shell nanoparticles for targeted cancer therapy without nanotoxicity,” Advanced Materials, vol. 26, no. 37, pp. 6436–6441, 2014.
- Z. Zha, S. Zhang, Z. Deng, Y. Li, C. Li, and Z. Dai, “Enzyme-responsive copper sulphide nanoparticles for combined photoacoustic imaging, tumor-selective chemotherapy and photothermal therapy,” Chemical Communications, vol. 49, no. 33, pp. 3455–3457, 2013.
- Y. Chen, C. Li, Z. Hou et al., “Polyaniline electrospinning composite fibers for orthotopic photothermal treatment of tumors in vivo,” New Journal of Chemistry, vol. 39, no. 6, pp. 4987–4993, 2015.
- Y. Chen, Z. Hou, B. Liu, S. Huang, C. Li, and J. Lin, “DOX-Cu9S5@mSiO2-PG composite fibers for orthotopic synergistic chemo- and photothermal tumor therapy,” Dalton Transactions, vol. 44, no. 7, pp. 3118–3127, 2015.
- J. Yu, D. Javier, M. A. Yaseen et al., “Self-assembly synthesis, tumor cell targeting, and photothermal capabilities of antibody-coated indocyanine green nanocapsules,” Journal of the American Chemical Society, vol. 132, no. 6, pp. 1929–1938, 2010.
- S. Zhang, Y. Li, X. He et al., “Photothermolysis mediated by gold nanorods modified with EGFR monoclonal antibody induces Hep-2 cells apoptosis in vitro and in vivo,” International Journal of Nanomedicine, vol. 9, no. 1, pp. 1931–1946, 2014.
- X. Liao and X. Zhang, “Preparation, characterization and cytotoxicity of carbon nanotubechitosanphycocyanin complex,” Nanotechnology, vol. 23, no. 3, 2012.
- P. Huang, Y. Gao, J. Lin et al., “Tumor-specific formation of enzyme-instructed supramolecular self-assemblies as cancer theranostics,” ACS Nano, vol. 9, no. 10, pp. 9517–9527, 2015.
- H. Yang, H. Mao, Z. Wan et al., “Micelles assembled with carbocyanine dyes for theranostic near-infrared fluorescent cancer imaging and photothermal therapy,” Biomaterials, vol. 34, no. 36, pp. 9124–9133, 2013.
- L. Wu, S. Fang, S. Shi, J. Deng, B. Liu, and L. Cai, “Hybrid polypeptide micelles loading indocyanine green for tumor imaging and photothermal effect study,” Biomacromolecules, vol. 14, no. 9, pp. 3027–3033, 2013.
- E. J. Lee, S. J. Lee, Y.-S. Kang et al., “Engineered proteinticles for targeted delivery of siRNA to cancer cells,” Advanced Functional Materials, vol. 25, no. 8, pp. 1279–1286, 2015.
- B. Li, X. Chu, M. Gao, and W. Li, “Apoptotic mechanism of MCF-7 breast cells in vivo and in vitro induced by photodynamic therapy with C-phycocyanin,” Acta Biochimica et Biophysica Sinica, vol. 42, no. 1, pp. 80–89, 2010.
Copyright © 2016 Sheng Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.