Table 2.

Nanotherapeutic approaches to target cellular components of tumor microenvironment for overcoming cancer drug resistance.

Nanoparticles Platform	Targeted Component of TME	Drug/Therapeutic Agent/Surface Functionalization	Outcomes	Reference
Lipid-nanoparticle composite	Tumor-associated fibroblasts (TAFs)	Single chain tumor necrosis factor (TNF)	Enhancement of specific uptake and activity of TNF nanocytes	[120]
PEGylated carboxymethylcellulose nanocomposite	Tumor-associated fibroblasts (TAFs)	Docetaxel	Several fold increase in circulation time, and tumor perfusion, reduction in metastasis	[121]
Polyethyleneimine-β-cyclodextrin (PEI-β-CD) complex	Tumor-associated fibroblasts (TAFs)	CY11 peptide	Two-fold higher gene delivery efficiency	[122]
Gold nanoparticles	Tumor-associated fibroblasts (TAFs)	Fibroblast growth factor 1 (FGF1)	40% reduction in cell viability	[123]
Cleavable amphiphilic peptide (CAP) nanoparticles	Tumor-associated fibroblasts (TAFs)	Fibroblast activation protein-α (FAP-α)	Disorganization of the stromal barrier, enhancement of local drug accumulation	[124]
Nanoparticle-based photoimmunotherapy (nano-PIT)	Tumor-associated fibroblasts (TAFs)	Fibroblast-activation protein (FAP)	Significantly enhanced T cell infiltration, and efficient tumor suppression.	[125]
Antibody-drug conjugate (ADC)	Tumor-associated fibroblasts (TAFs)	Tumor endothelial marker 8	Blocked metastatic growth, and prolonged overall survival.	[126]
Conjugated nanoparticulate system	Tumor-associated fibroblasts (TAFs)	Cisplatin, siWnt16	Knockdown of Wnt16	[127]
Poly (lactic-co-glycolic acid) (PLGA)	Tumor-associated fibroblasts (TAFs)	Rapamycin	Modulation of tumor vasculature	[128]
Nanohydrogel particles and lipoplexes	Tumor-associated fibroblasts (TAFs)	Cyclic peptide and siRNA	Enhanced in vivo uptake, functional siRNA delivery	[129]
PLGA nanoparticles conjugated with Arginine-glycine-aspartic acid (RGD)	Tumor-associated vascular endothelial cells	Paclitaxel (PTX) and combretastatin A4 (CA4)	Tumor vasculature disorganization, inhibition of cell proliferation, significantly enhanced apoptosis	[130]
PEG-PLA nanoparticles	Tumor-associated vascular endothelial cells	F3 peptide	Deep penetration at the tumor side, Enhanced accumulation with longest survival	[131]
Nanographene oxide nanocomposite	Tumor-associated vascular endothelial cells	TRC105, a monoclonal antibody that binds to CD105	Improved uptake at tumor site	[132]
Polyacrylic acid (PAA)-coated superparamagnetic iron oxide	Tumor-associated vascular endothelial cells	RGD	Tumor targeting and antiangiogenic response	[133]
Cholesterol-based nanoparticles	Tumor-associated vascular endothelial cells	Doxorubicin (Dox) and RGD	15-fold increase in antimetastatic activity	[134]
Gold nanorods	Tumor-associated vascular endothelial cells	RGD	Downregulation of integrin α(v)β₃ expression	[135]
PEG nanoparticles	Tumor-associated macrophages (TAMs)	Mannose	Efficient targeting of TAMs	[136]
Polymer nanoparticles	Tumor-associated macrophages (TAMs)	Mannose and siRNA	Enhanced uptake and efficient delivery of siRNA	[137]
PLGA nanoparticles	Tumor-associated macrophages (TAMs)	Antigenic peptides, hgp100 (25–33) and TRP2 (180–188)	Significantly delayed growth of melanoma	[138]
PLGA-based nanoparticles	Tumor-associated T cells	Inhibitor of transforming growth factor beta receptor 1 (TGFβR1)-R848	Promotes infiltration of T cells, improved efficacy for delivery	[139]
PLGA-based nanoparticles	Tumor-associated antigen presenting cells	anti–PD-1 monoclonal antibodies	Increase in expression of adhesion molecules, enhance antitumor immunity	[140]
Lipid-coated calcium phosphate nanoparticles	Tumor-infiltrating T-lymphocytes	siRNAs against PD-1 and PD-L1	Effective delivery of siRNAs, silencing of PD-1 and PD-L1 expression, improved cytotoxicity	[141]
Poly(lactic-co-glycolic) acid (PLGA) nanoparticles	Tumor-infiltrating T-lymphocytes	Indocyanine green (ICG), imiquimod (R837)	Checkpoint-blockade, effective immunotherapy	[142]
Polymer nanoparticles	Tumor-associated leukemia-specific T cells	DNA	Effective targeting of chimeric antigen receptors (CARs), long-term disease remission	[143]
Liposome nanoparticles	Tumor-infiltrating lymphocytes (TIL)	Antagonist for the adenosine receptor A2A (SCH-58261)	Controlled drug effects on cells, enhanced active targeting	[144]
TH10 peptide nanoparticles	Tumor-associated pericytes	Docetaxel	Pronounceable pericyte apoptosis induction	[145]
Liposome nanoparticles	Tumor-associated lymphatic vessels	Doxorubicin, cyclic peptide (LyP-1)	Increased liposome uptake, reduction in metastasis	[146]