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. 2025 Jul 11;17(7):899. doi: 10.3390/pharmaceutics17070899

Table 4.

Overview of nanoparticles carrying therapeutic genes.

S.No. Nanomaterial Structure Targeting Moiety Molecular/Cellular Target Cargo Mechanism of Action Animal Model/Cell Line Outcomes Adverse Events Reference
1 T-M/siRNA micelle (CSKC-PEG-pArg-pLys-SS-PTX)

  • CSKC peptide

  • PEG

  • Disulfide bond

  • Polyarginine

  • Polylysine

 CSKC peptide IGF-1R/BBB/tumor cells

  • PCDH 7-targeting siRNA

  • Paclitaxel

  • CSKC peptide of NPs bind to IGF-1R on the surface of BBB`s endothelial and tumor cells helping NP passing BBB and targeting tumor cells.

The micelles release the free drugs PTX and siRNA in a high GSH environment of tumor. siRNA targets PCDH 7 of GJs, disrupting communication between astrocytes and BM. PTX targets BM.

  • Nude mice

  • MDA-MB-231/Luc

  • Enhanced cellular uptake

  • Decreased expression of PCDH 7 and GJs between BM cells and astrocytes

  • Enhanced in vitro cytotoxicity

  • Improved survival in treated mice

 None [105]
2 Modified MN (MN-anti–miR-10b)

  • Magnetic NP

  • Near infrared dye (Cy5.5-NHS)

  • Linker SPDP

 cyclic RGDfK (cRGD) αvβ3/αvβ5 integrins/BBB/tumor cells anti–miR-10b cRGD-integrin mediated endocytosis of MN-anti–miR-10b. anti–miR-10b targets upregulated miRNA-10b in BM, disrupting its role in BM.

  • Balb/c nude mice

  • MDA-MB-231-BrM2-831 cells

  • NPs cross the BBB and accumulate in BM.

  • BM-bearing mice treated with MN-anti–miR-10b showed marked regression of tumor lesion compared to control group treated with only MN.

 None [109]
3 Engineered exosome (ExoscFv) Same as exosome

  • Lipid

  • protein

 anti-EGFR scFv-lamp2b EGFR/tumor cells LPCAT1-targeting siRNA Exosomes are biological NP, so they passively cross the BBB. But the anti-EGFR scFv-lamp2b selectively bind to EGFR on the surface of BM.

  • BALB/C nude mice

  • HEK293T cells and PC9 cells

 Reduced BM burden in mice treated Weight loss in treated mice [114]
4 T-siHER2-NP(DTX)

  • PEI

  • MSNP

  • PEG

  • TRZ

TRZ HER2 Receptors

  • Docetaxel (DTX)

  • HER2 siRNA

  • TRZ

  • Focused ultrasound-based BBB penetration of NP.

  • TRZ targets HER2 on tumor cells.

  • siRNA inhibits the synthesis of HER2 protein.

  • SCID female mice

  • BT474/HCC1954/MCF7 cell lines

  • LM2-4luc+H2N/BTGFL1 cell lines

  • The majority of the HER2+ cell line (BT474) underwent apoptotic death.

  • Mice treated with MB-FUS plus T-siHER2-NP(DTX) showed inhibition of intracranial BTGFL1 tumor growth.

 None [115]
5 AP30NP
Poly(lactone-co-β-amino ester)

  • PDL

  • MDEA

  • TDDP

  • AMD3100

  • PEG

 AMD3100 CXCR4/tumor cells proMel gene AMD3100-CXCR4 interaction based tumor target.
proMel Gene synthesize secretory promelittin, which is converted to melittin by MMP in TME. Melittin is tumor cytolytic.

  • Female nude mice (NCr nu/nu)

  • NHA/231BR cells

  • significantly inhibited tumor progression in vivo.

  • increased cellular apoptosis in tumors.

  • No significant damage to normal brain tissue around tumors.

 None [118]

CSKC = cysteine-serine-lysine-cysteine, IGF-1R = insulin-like growth factor 1 receptor, PEG = polyethylene glycol, GSH = glutathione, GJs = gap junctions, SPDP = N-succinimidyl 3-[2-pyridyldithio]-propionate, MN = magnetic nanoparticle, RGDfK = Arg-Gly-Asp-D-Phe-Lys, EGFR = epidermal growth factor receptor, MSNP = Mesoporous silica NP, PEI = polyethyleneimine, TRZ = trastuzumab, MB-FUS = microbubble-assisted focused ultrasound, PDL = ω-pentadecalactone, MDEA = N-methyldiethanolamine, TDDP = diethyl 3,3′-(4,4′-trimethylenedipiperidine-1,1′-diyl) dipropionate.