Table 6.

Overview of the nanoparticles carrying tumor microenvironment modulators.

S.No.	Nanomaterial	Structure	Targeting Moiety	Molecular/Cellular Target	Cargo	Mechanism of Action	Animal Model/Cell Line	Outcomes	Adverse Events	Reference
1	Lasomes	Liposome CM of RA CM of BM cell	Portion of CM of RA and/or BM cells	CM of RA and/or BM cells	carbenoxolone	Las, being biomimetic, use homotypic CM recognition mechanism to carry CBX to astrocytes and BM cells, blocking GJs between them, enhancing DNP chemosensitivity.	C57BL/6 mice LLC-BrM cell line	Improved survival in treated mice Decreased tumor progression in treated group Favorable biocompatibility and biosafety.	None	[127]
2	P5091@RMPs-R4F	Same as microvesicles R4F peptide	R4F peptide	SR-B1 receptor/BBB/TAM	P5091 (USP7 inhibitor)	R4F peptide binds SR-B1 receptor, mediating P5091@RMPs-R4F cross the BBB and targeting M2. P5091 reverses immune-suppressive TME.	C57BL/6 female mice bEND.3 cells LLC Cell Line BV2 cells	Increased BBB crossing in vitro as well as in vivo. Prolonged survival in mice.	NS	[135]
3	R&B/NP	PLGA core coated with erythrocyte and MDA-MB-231Br hybrid cell membranes	Hybrid membrane (erythrocyte + 231Br cell membrane)	CM of Inflammatory BBB/tumor cells	Dexamethasone (Dex), Embelin (Emb)	Hybrid membrane, being biomimetic, use homotypic CM recognition to target the BBB and tumor cells. Inhibits secretion of serpin B2 and neuroserpin to restore plasmin activity, plasmin cleaves L1CAM and converts FasL to sFasL, leading to apoptosis and blocking vessel-associated spread	BALB/c nude mice MDA-MB-231Br cells/bEND.3/RAW264.7 macrophages/BV2 microglia/HT22 neurons	Significantly reduced intracranial tumor growth prolonged survival (median 46.5 vs. 26 days) increased apoptosis and decreased L1CAM expression	None	[130]
4	NI@I-NP: Physical combination of two ICAM-1-targeted NP: NTZ@I-NP and IBR@I-NP	PLGA-PLL NP functionalized with ICAM-1-targeting γ3 peptide via PEGylation	ICAM-1-targeting γ3 peptide	ICAM-1 on BTB endothelial cells and tumor pericytes	NTZ@I-NP loaded with Nitazoxanide I@I-NP loaded with Ibrutinib	NP selectively binds to ICAM-1 on BTB Nitazoxanide inhibits WNT signaling resulting TJs opening Ibrutinib inhibit BMX, depleting neoplastic pericyte to synergistically and specifically open the BTB	BALB/c nude mice 231Br (HER2+ brain-seeking breast cancer cells)	Sequential drug release of NTZ then IBR opens BTB Median survival improved: 49 days with Dox+NI@I-NP (compared to free Dox, p < 0.0001 and NI@I-NP, p = 0.0005) and 46.5 days with ETO+NI@I-NP (vs. free ETO, p = 0.0002 and NI@I-NP, p = 0.0005)	None	[136]

CM = cell membrane, RA = reactive astrocytes, BM cells = brain metastatic cells, LAs = LAsomes, GJs = gap junctions, CBX = carbenoxolone, DNP = docetaxel-loaded human serum albumin nanoparticles, LLC = Lewis lung carcinoma, BV2 cells = murine (mouse-derived) microglial cell line, USP7 (ubiquitin-specific protease 7), TAM = tumor associated macrophages, NS = not specific, PLGA = poly(lactic-co-glycolic acid), BMX = bone marrow and X-linked nonreceptor tyrosine kinase, BTB = blood–tumor barrier.