Nanotechnology in the Treatment of Diabetic Complications: A Comprehensive Narrative Review

Table 1

Common complications of diabetes mellitus and application of nanotechnology.

Author and year of literature	Complication	Application of nanotechnology	Functional route	Advantage	Disadvantage or notes
Yang, 2019 [46]	Diabetic nephropathy	Formulation of crocetin-loaded PLGA nanoparticles	Downregulated the production and expression of fibrotic factors viz., TGF-β1 and fibronectin and inflammatory cytokines including MCP-1 and TNF-α in renal; abated NF-κB expression activation and PKC activity	Antifibrosis and anti-inflammatory effects	Only for animal experiments now
Ahangarpour, 2019 [47]	Diabetic nephropathy	Myricetin solid lipid nanoparticles (SLN)	Reducing oxidative stress and increasing antioxidant enzyme levels	The form of nanoparticles can improve the drug effect	Only for animal experiments now
Ahad, 2018 [48]	Diabetic nephropathy	The nanoliposomes containing Eprosartan mesylate	Renal protection by decreasing serum creatinine, urea, lactate dehydrogenase, and total albumin	Lowering blood pressure; reducing the degree of fibrosis	Only for animal experiments now
Fangueiro, 2015 [50]; Jo, 2012 [51]	Diabetic retinopathy	Silicate (SI) nanoparticles	Inhibited VEGF-induced phosphorylation of VEGFR-2 in HRMECs	Inhibition of retinal neovascularization, nontoxic	Could be considered to use in clinical treatment
Fangueiro, 2015 [50]; Kim, 2011 [52]	Diabetic retinopathy	Gold nanoparticles	Suppresses VEGFR-2 autophosphorylation followed by blocking ERK 1/2 activation and suppresses VEGFR-2 signaling pathway	Effective inhibition of retinal neovascularization, nontoxic	Could be considered to use in clinical treatment
Fangueiro, 2015 [50]; Jo,2012 [51]	Diabetic retinopathy	Titanium dioxide (TiO2) nanoparticles	Inhibited VEGFR-2/MAPK pathway, not affecting PI3K/Akt pathway	Intravitreal injection can effectively inhibit retinal neovascularization	Could be considered to use in clinical treatment
Fangueiro, 2015 [50]; Gurunathan, 2009 [54]	Diabetic retinopathy	Silver nanoparticles	Targeting the activation of PI3K/Akt signaling pathways	Inhibition of VEGF induced angiogenesis	Only for animal experiments now
Luyan, 2018 [58]	Diabetic cardiomyopathy	PSS-NP	Upregulation of PI3K/Akt/eNOS/VEGFA signaling pathway	Improve heart function, regulating the ultrastructure of microvascular endothelial cells, reduce vascular endothelial injury	Only for animal experiments now; the optimal dosage needs to be determined
Zhang, 2017 [59]	Diabetic cardiomyopathy	FGFl nanoliposomes combined with UTMD	Low-frequency ultrasound combined with microbubbles	Improve myocardial function, improve the apoptosis of cardiac cells, increase myocardial blood flow	Could be considered to use in clinical treatment; new targeted therapy
Asadi, 2019 [62]	Peripheral	Nanocurcumin on the severity of sensorimotor polyneuropathy (DSPN)	Inhibits production of proinflammatory cytokines including TNF-α and interleukin-1 (IL-1), and also prevents synthesis of NO	Reduces mechanical, heat, and pain allergies	Applied to clinical trials; need future long-term studies with different dose
Luo, 2019 [63]	Peripheral	Nano-miR-146a-5p	Inhibits the inflammatory response and apoptosis to reduce DPN by regulating the NF-κB signaling pathway	Regulates inflammatory reaction and apoptosis, protects peripheral nerve	Only for animal experiments now; other potential mechanisms still need to be explored
Gainza, 2013 [67]	Diabetic foot	rhEGF-NPS	Induced the fibroblasts to proliferate and migrate	Accelerating the proliferation of fibroblasts	Animal experiments are limited; further research on human experiments is needed
Chen, 2012 [87]; Leu, 2012 [68]	Diabetic foot	AuEA	Anti-inflammation and angiogenesis modulation	Reduces RAGE expression in fibroblasts and promote wound healing	Could be considered to use in clinical treatment
Liu, 2018 [70]	Diabetic foot	CNPsGMs/hydrogel	The GMs containing CNPs were loaded into the thermos-sensitive hydrogel responding to the MMPs that usually overexpress	Accelerates wound healing and collagen formation and improves neovascularization	Could be considered to use in clinical treatment
Sonamuthu, 2020 [71]	Diabetic foot	L-carnosine	Inhibition of MMP-9 activity and growth of bacteria; anti-inflammatory, ROS-scavenging, and antioxidant	Better wound contraction	Could be considered to use in clinical treatment
Gao, 2017 [72]	Diabetic foot	The inner loaded DMOG composite nanofiber membrane	Promotes the process of wound healing, promotes the reepithelialization and vascularization of the wound	Similar to that of natural extracellular matrix; has drug-controlled release effect	Could be considered to use in clinical treatment
Tian, 2012 [74]	Segmental bone injury	nHAC	Bone defect filling; provide framework for new bone	Shorten operation time, promote fracture healing and improve source problems	Applied to clinical trials
Ren, 2019 [75]	Segmental bone injury	Adiponectin nano	Increased the ALP activity of osteoblasts; induced more collagen secretion; promoted the expression of osteogenic related genes and their corresponding proteins	Increased ALP activity, induced collagen secretion, and extracellular matrix mineralization	Only for animal experiments now
Tang, 2019 [85]	Male fertility decline	ZnONP	Regulate DNA methylation via activating NRF1 and SIRT1	Improve sperm quantity and activity, increase serum testosterone level	Only for animal experiments now; treatment of female reproductive disorders needs to be evaluated
Liu, 2017 [79]	Diabetic macroangiopathy	Nanoselenium	Reducing oxidative stress injury of injured cells	Low concentration of nanoselenium can resist oxidation	Only for animal experiments now; treatment of female reproductive disorders needs to be evaluated