Table 2.

Studies on Chitosan-based Nanoparticles of Targeted Drug Delivery Systems.

Chitosan Composition	Agents of Drugs	Preparing Method	EPR Effect	Activ Targeting Receptor	BC Cell Line	Effect	Reference
Carboxymethyl dextran (CMD) Chitosan nanoparticles (ChNPs)	Co-delivery of IL17RB siRNA and DOX	The Ionic gelation Method	d = 114 nm size, PDI = 0.3 and zeta potensial = 10.1 mV		MDA-MB361 cells	A significant silencing of NF-kB and Bcl-2 relative gene expression, apoptosis induction and migration inhibition	[66]
Glycol-chitosan-coated gold nanoparticles(GC-AuNPs)	AuNPs	Ethylene glycol moieties, substituting chitosan’s hydroxyl groups.	d = 94.4646.45 nm. zeta potensial 37.44.4 mV		MDA-MB-231	Enhanced cellular uptake, tumor accumulation, improved tumor-targeting of GC-AuNPs	[67]
Histidine-grafted chitosan-lipoic acid NPs (HCSL-NPs) were	doxorubicin (DOX)	Congujation	D = 106.0 nm, Z = −25.0. PDI = 0.129		4T1 cells	Enhanced internalization at extracellular pH, rapid release of intracellular drugs, and improved in vitro cytotoxicity against 4T1 cells were shown.	[34]
D-alpha-tocopherol polyethylene glycol 1000 succinate conjugated chitosan (TPGS-g-chitosan)	Docetaxel, Trastuzumab	Combined modified solvent evaporation technique with ionic cross-linking	186 nm 1.41 ± 0.20 mV	HER-2 receptor targetted	SK-BR-3	Cellular uptake and cytotoxicity have been enhanced. Increase in AUC and prolonged circulation of 1.4793 and 0.2847 μg/mL and greater safety than Docel TM.	[57]
Multifunctional hyaluronic acid/hydroxyethyl chitosan nanocomplexes	doxorubicin and 5-aminolevulinic acid.	Self-assembly method.	140 nm −24.6 mV, near-spherical shaped	The anti-HER2 antibody targeting moiety	MCF-7	Enhanced the cellular uptake, displayed pH-responsive surface charge reversal, and drug release.	[68]
Aldehyde hyaluronic acid (AHA) and hydroxyethyl chitosan (HECS)	Doxorubicin (DOX) and cisplatin	Conjugation and Self-assembly.	∼160 nm. −28 mV near- spherical morphology	HER2 receptor	MCF-7	The cellular uptake of the nanoplatforms was significantly improved by HER2 receptor-mediated active targeting. Improved stability.	[69]
Encapsulated O-succinyl chitosan graft Pluronic® F127 (OCP) copolymer nanoparticles	Doxorubicin (DOX) with an anti-HER2 monoclonal antibody	Conjugated And Ionic cross-linking agents.	d = 34.92–48.79 nm	HER2 receptor	MCF-7	At pH 5.0.0, the drug was quickly and fully released from the nanoparticles. It improved cytotoxicity and selectivity. High efficiency of encapsulation.	[70]
Chitosan and pectin	Ribosome-inactivating protein (RIP)	polyelectrolytes complex and conjugation process with antiEpCAM antibody	376.8 nm + 36.05 mV with index polydispersity of 0.401	epithelial cell adhesion target	T47D and Vero cell lines	Increased the cytotoxicity of RIP. Low selectivity.	[71]
Low viscosity Chitosan and alginate	Ribosome-inactivating protein (RIP) from M. Jalapa L. leaves (RIP)	conjugated with anti-EpCAM antibody	D = 130.7 nm, +26.33 mV polydispersity index of 0.380	epithelial cell adhesion target	T47D Breast Cancer Cell Line	Enhance cytotoxicities, less selectivity.	[72]
The copolymer of chitosan and polyethylene glycol (PEG)	Superparamagnetic iron oxide nanoparticle (SPION) and fluorescent dye	A derivative of chitosan and Chitosan and polyethylene glycol (PEG) copolymer-coated conjugated SPIONs were labeled for optical detection and conjugated with a monoclonal anti-neu-receptor antibody (NP-neu).	Z = 44 and small PDI values	a monoclonal antibody at neu receptor (NP-neu).	mouse mammary carcinoma (MMC) cells	In MR images of primary breast tumors, significant contrast enhancement was provided, and high uptake was shown.	[73]
Folic acid-gallic acid-N, N, N-trimethyl chitosan (FA-GA-TMC)	cubic-like selenium nanoparticles (SeNPs)	Conjugation and the self-assembly method.	D = 300 nm, 30.1 mV.	Folic acid receptor	Cancer cells and normal cells (WI-38)	Improved anticancer efficacy and cellular uptake against breast cancer cells while demonstrating good selectivity.	[56]
Poly(N-vinylcaprolactam) (PNVCL)-chitosan (CS) nanoparticles (NPs).	doxorubicin (DOX) and cell-penetrating peptide	Conjugation and self-assembly	D = 120 ± 15 nm (n = 8). Z = −12.5 ± 2.5 mV. low polydispersity.	Cell-penetrating peptide (CPP)	MCF-7 TNB breast cancer cell line	Improved cytotoxicity, showing a selective reduction in tumor volume and prolongation of life span.	[45]
PEGylated chitosan and poly-L-arginine.	Superparamagnetic iron oxide nanoparticles (SPION) and siRNA	Conjugation and self-assembly	HD (nm) 213 ± 36 0.43 ± 0.05 Z = 30.7 ± 1.4	Cell-penetrating peptide (CPP)	MDA-MB-231 triple-negative breast cancer cells.	show a high uptake, the efficacy of the siRNA retention and protection, downregulation of GFP expression.	[74]
Oxidized hyaluronic acid-decorated dihydroxy phenyl/hydrazide bifunctionalized hydroxyethyl chitosan (DHHC)	gold nanorod (GNR) and Doxorubicin (DOX)	Congujation, chitosan derivates.	D = 94.0 nm, Z = +25.3 mV	Hyaluronic acid	MCF-7 cells	Enhanced cellular uptake and enhance cytotoxicity	[75]
Chitosan and alginate nanocapsules	Iron-saturated bovine lactoferrin (Fe-bLf)	Polyelectrolyte	Spherical size and d = 322 ± 27.2, z = −1.29 mV, PDI = 0.084	Low-density lipoprotein receptor and transferrin receptor	MDA-MB-231	Improved antitumor activity in breast cancer by internalizing and regulating micro-RNA expression via the low-density lipoprotein receptor and transferrin receptor.	[76]