Targeted Therapeutic Nanoparticles: An Immense Promise to Fight against Cancer

Table 1

A brief overview and purposes of various actively targeted delivery systems using PLGA and PEG to their suitable targets.

Target cells/diseases/animal models	Targets	Targeted delivery system	Purpose of the study	Reference
(I) Transferrin ligand
Leukemia (K562 cells)	Transferrin	Daunorubicin loaded PLGA-polylysine-PEG-transferrin	(i) To assess the antitumor efficacy of the delivery system with or without Daunorubicin/transferrin in vitro and in vivo	[41]
Brain capillary endothelial cells (BCEC) and astrocytes	Transferrin	PLGA NPs coated with bovine serum albumin/transferrin	(i) Evaluation of possible endocytosis mechanism for transferrin targeted brain drug delivery	[42]
Swiss albino mouse (female or male)	Transferrin	Lamotrigine loaded PLGA NPs	(i) Surface functionalization of NPs using transferrin and lactoferrin as ligand to deliver Lamotrigine to brain; (ii) The purpose was to improve the biodistribution and pharmacokinetic profile of drug as well as reduced accumulation in nontargeted organs (kidney, lung, liver, spleen, heart) of the mouse	[43]
Pancreatic cancer cells	Transferrin	Bortezomib loaded PLGA NPs	(i) To study the targeting efficiency and capacity of transferrin targeted NPs	[44]
Breast cancer and glial cells	Transferrin	Curcumin/5-fluorouracil loaded magnetic PLGA NPs	(i) To identify the mechanism of cell death by the dual drug transferrin targeted NPs; (ii) To identify the effect of magnetic hyperthermia to destroy cancer cells	[45]
Brain glioma cells	Transferrin	Paclitaxel and Doxorubicin loaded magnetic silica PLGA NPs	(i) To determine the transport efficiency through blood-brain barrier and target glioma cancer cells; (ii) To investigate the therapeutic efficiency of targeted NPs in tumor bearing balb/c mice	[46]
(II) Small peptides
(1) Asparagine-glycine-arginine (NGR/RGD)
Human fibrosarcoma cell line (HT-1080) and human umbilical vein endothelial cells (HUVEC)	Aminopeptidase N (CD13)	Docetaxel loaded PLGA-PEG diblock copolymer NPs	(i) Exploration of the targeting potential of the drug loaded PEG-PLGA NPs in vitro cell lines; (ii) Evaluation of hematologic toxicity, antitumor efficacy, nephrotoxicity and hepatotoxicity in balb/c mice	[47]
(2) cLABL peptide against ICAM-1
A549 lung epithelial cells	Intercellular adhesion molecule-1 (ICAM-1)	Modified Pluronic® surfactant on PLGA NPs	(i) To find how NPs are targeted to lung epithelial cells via ICAM-1 to be internalized	[48]
(3) Cyclo-arginine-glycine-aspartate (c-RGD) and combinations
Choroidal neovascularization (CNV) induced rat	Integrin/Transferrin	Antivascular endothelial growth factor intraceptor, Flt23K loaded PLGA-RGD/transferrin and/or PLGA-RGD-transferrin NPs	(i) To apply the targeted delivery of peptide modified PLGA NPs for the management of CNV, the cause of blindness due to macular degeneration	[49]
Human pancreatic cancer and human glioblastoma	Integrin β3	c-RGD-modified micelle-type PLGA-4-arm PEG	(i) To prove the use of multi-branched PLGA micelle as a diagnostic probe for pancreatic tumor detection	[50]
HUVEC cells	Integrin β3	Paclitaxel loaded PLGA-PEG NP or PEG-PCL (polycaprolactone) NP	(i) To investigate the effect of RGD peptide to target tumor endothelium and to see the antitumor efficacy of Paclitaxel	[51]
(III) Folic acid and folic acid combinations with other ligands
Glioblastoma multiforme	Folate/lactoferritin	Folic acid or lactoferritin modified Etoposide encapsulated PLGA NPs	(i) Assessment of anti-tumor efficacy of Etoposide when encapsulated in the ligand-PLGA conjugate; (ii) Identification of the expressions of folate and lactoferritin receptors in target cells	[52]
Human epidermal carcinoma cells	Folate	PLGA-folate and PLGA-RGD	(i) To confirm that surface modified NPs showed effective cellular uptake with no cytotoxicity	[53]
Human breast cancer cells (MCF-7)	Folate	Vincristine sulphate loaded PLGA-PEG-folate NPs or PLGA-PEG-cell penetrating peptide R7	(i) To investigate the cell uptake capacity of the ligand-drug-PLGA conjugate and ligand-PLGA conjugate; (ii) To evaluate the tumor targeting and antitumor efficacy in in vivo model	[54]
Colorectal cancer	Folate	Folate modified Capecitabine loaded PLGA-PEG NPs and flate-PLGA-PEG NPs	(i) To prepare the two blends of NPs to evaluate their control release properties	[55]
Cervical tumor cells and human ovarian cancer cells	Folate	Folate modified Quercetin loaded PLGA-PEG NPs	(i) To test the cytotoxicity profile, targeting effect and cell uptake properties of the folate expressing cancer cells; (ii) To demonstrate the active tumor targeting of folate bearing NPs	[56]
(IV) Antibodies
SKBR-3 breast cancer cell	HER2	Anti-HER 2 trastuzumab antibody -modified Docetaxel-loaded PLGA	(i) To point out the feasibility of ligand conjugation strategy and demonstrate its efficiency in cell uptake and cytotoxicity	[57]
MCF-7 breast cancer cell	HER2	Anti-HER 2 trastuzumab antibody -modified human serum albumin NPs or gelatin NPs	(i) To observe the specific targeting of Herceptin conjugated NPs to Her2 overexpressed cells	[58]
Melanoma hepatocellular carcinoma and breast cancer cell	SM5-1 binding protein	Paclitaxel loaded PLGA linked with SM5-1 single chain antibody (scFv) derived from SM5-1 monoclonal antibody	(i) To develop the targeted NP system and examine their specific binding, cross-reactivity and internalization; (ii) To evaluate the in vitro cytotoxicity effect of Paclitaxel loaded targeted NPs	[59]
Metastatic lesion of human prostatic adenocarcinoma	Androgen receptor (AR) and β-catenin	PSMA antibody conjugated PLGA-Curcumin NPs	(i) To generate an antibody conjugated targeted NP to target Ar/β-catenin in order to inhibit tumorigenesis	[60]
PSMA positive prostate cancer cell	PSMA positive cell surface	PLGA-PEG copolymer derived microbubble (MB) conjugated with urea based PSMA inhibitor molecular probe	(i) To establish the MB-molecular probe conjugate and confirm their selective binding to PSMA positive cells	[61]
(V) Aptamer
PSMA on the surface of prostate cancer cell	PSMA	PLGA-PEG-Aptamer A10 triblock NPs	(i) To determine the optimum surface density of aptamer on the NP surface for maximum uptake by prostate cancer cell both in vivo and in vitro	[62]
Carbohydrate and polysaccharide
Dendritic cell	Mannose receptor	Mannan-decorated PLGA NPs	(i) To incorporate mannose by covalent conjugation and adsorption method, compare the methods based on uptake of NPs by cells	[63]
Lung epithelium adenocarcinoma and human pulmonary microvascular endothelial cells	Hyaluronic acid (HA) receptor for HA NPs, for other systems it is not elucidated	Glycosaminoglycan such as heparin, HA, chondroitin sulfate and dermatan sulfate modified PLGA NPs	(i) Evaluation of the toxicity profile of the NP systems; (ii) To validate the systems for lung cancer treatment	[64]
(VI) Other ligands: nuclear localization signal (NLS) peptide
Breast cancer cell (MCF-7)	Cell nucleus	Doxorubicin loaded NLS-conjugated PLGA NPs	(i) To increase the concentration of Doxorubicin in cell nucleus via NLS targeted NPs; (ii) To study the antiproliferative activity of targeted NPs and nontargeted NPs	[65]