In vivo evaluation of therapeutic outcomes and toxicity of nanomaterialsa.
| Nanomaterial | Drug, bioactive, photosensitizer, or gene | Therapeutic strategy | Animal model/cell line | Bio-distribution | Tumor growth inhibition (tumor ablation, recurrence) | Survival rate | Antileukemic efficacy of the nano-drug | Side effects (systematic toxicity, body weight, and histologic assessment) |
|---|---|---|---|---|---|---|---|---|
| Liposome163 | Vincristine (VCR) | Liposomal vincristine 50–60 nm, 1 mg kg−1 intraperitoneal | Xenograft NOD/SCID mice, B-ALL | ND | 20% delay in tumor progression | Increased lifespan | Enhanced Antileukemic efficacy compared to the free drug | Well tolerated, safer |
| Liposome161 | cytarabine : daunorubicin cocktail (300 : 4.5 mg kg−1) | CPX-351: Cyt : Daun 100 ± 20 nm, 10 : 4.4 mg kg−1 i.v. | SCID/Rag2M mice, CCRF-CEM | Considerable and constant tumor uptake (BM) | ND | Increased lifespan | Enhanced Antileukemic efficacy compared to free-drug cocktail | ND |
| Liposome162 | cytarabine : daunorubicin cocktail (300 : 4.5 mg kg−1) | CPX-351: Cyt : Daun 10 : 4.4 mg kg−1 i.v. | Xenograft Rag2-M mice, CCRF-CEM | Considerable and constant tumor uptake (BM) | Long-term remission in 33% of mice | Increases lifespan | Enhanced Antileukemic efficacy with consolidation compared to induction therapy alone, enhanced Antileukemic efficacy compared to free-drug cocktail | Severe and prolonged cytopenia, slow BM recovery |
| Liposome-PEG87 | WHI-P131 (CAS 202475-60-3) JAK3 tyrosine kinase inhibitor/vincristine (VCR) 0.050 mg kg−1 | WHI-P131-NP 100 nm, 100 mg kg−1 day−1 × 2 days i.p. | Xenograft SCID mouse, resistant B-ALL RS4; 11 | ND | No signs of overt leukemia | Increased lifespan | Enhanced Antileukemic efficacy compared to the free drug and vincristine (VCR) | ND |
| Liposomal Nanoformulation (LNF)-PEG146 | TBI treatment (200y γ-rays) | C61-LNP 136.3 ± 1.2 nm, 80 mg kg−1 i.v./C61-LNP + 2 Gy γ-rays | Xenograft NOD/SCID mouse, relapsed BPL xenograft NOD/SCID | ND: favorable pharmacokinetic of 25A145 | ND | Increased lifespan | Enhanced Antileukemic efficacy compared to the free drug | Well tolerated, safer |
| TBI treatment (400y γ-rays) | C61-LNP 136.3 ± 1.2 nm, 80 mg kg−1 i.v./C61-LNP + 4 Gy γ-rays | CD22ΔE12×BCR-ABL double-Tg mice, radiation-resistant BPL | Lower tumor growth/burden rate remission C61-LNP + TBI mice: 100%, TBI: 50%, C61-LNP: (0) | Increased lifespan | Enhanced Antileukemic efficacy compared to the free drug | |||
| Liposome-PEG109 | Vincristine (VCR) | Sgc8-VCR-Lipo/VCR-Lipo 100 nm i.v. | Female BALB/c nude mice, CCRF-CEM | Liver, tumor accumulation | Lower tumor growth/burden rate | Increased lifespan | Enhanced Antileukemic efficacy compared to the free drug | Well tolerated, safer |
| PEG-PCL-ECT2 (amphiphilic block copolymers)17 | Dexamethasone (Dex) | Dex-NP-PEG 110 nm, 5 mg kg−1 i.v. | Xenograft NSG-B2m mice, human ALL | Spleen, liver accumulate, sustained plasma circulation, lower levels in the kidney and lung (clearance organs) | ND | Increase lifespan | Enhanced Antileukemic efficacy compared to the free drug | Well tolerated, safer |
| Amphiphilic block copolymers-PEG-PCL133 | DOX (doxorubicin) | Anti-CD19-DOX-NPs 75 nm, 2.5 mg kg−1 i.v. | Xenograft NSG-B2m mice, RS4; 11 B-ALL | BALB/c mice: liver, spleen accumulation (targeted NPs) with lower levels in clearance organs | ND | Increased lifespan | Enhanced Antileukemic efficacy compared to the free drug | Well tolerated, safer |
| PEG poly(lactic-co-glycolic acid)144 | IRAK1/4 and ABT-737 cocktail | IRAK/ABT-PEG-PLGA polymer NP 100 nm, 10 mg kg−1 IRAK inhibitor and 40 mg kg−1 ABT-737 | Xenograft female NPG mice, Jurkat | ND | Lower tumor growth/burden rate | Increased lifespan | Enhanced Antileukemic efficacy compared to the free drug | ND |
| Polyrotaxane-based nanoconstruct (PRNC), PEG108 | DOX (doxorubicin) | Sgc8-DOX-PRNCs-PEG i.v. | Balb/c nude mice, CCRF–CEM | ND: rapid clearance of NPs | Lower tumor growth/burden rate | ND | Enhanced Antileukemic efficacy compared to the free drug | Well tolerated, safer |
| Silver (AgNPs)-mesoporous silica nanospheres (MSNs)-PEG121 | Paclitaxel (PTX) | Sgc8-PTX-MSNs-AgNPs-PEG 90 nm, i.v. 1 mg kg−1 | BALB/c nude mice, CEM | Tumor accumulation | Lower tumor growth/burden rate | ND | Enhanced Antileukemic efficacy compared to the free drug | Well tolerated, safer |
| Polymeric micelles (PCL-ss-Sgc8-BSA (polycaprolactone)120 | Ara-C 20 mg kg−1 | Sgc8-PCL-ss-Ara-BSA 165.1 ± 5.2 nm, 20 mg kg−1 i.v. | Tumor-bearing mice, CCRF-CEM | ND | Lower tumor growth/burden rate | Increased lifespan | Enhanced Antileukemic efficacy compared to the free drug | Well tolerated, safer |
| Poly(beta-amino ester) (PBAE) polymer-(microtubule132 | Plasmid DNA encoding the leukemia-specific 194-1BBz CAR (+iPB7 transposase). Infusion of 194-1BBz CAR-T cells transduced ex vivo with 194-1BBz-encoding lentivirus vectors | anti CD3-antiCD19-194-1BBz CAR-(PBAE)-(MTAS)-(NLS) i.v. | Albino C57BL/6 mice, B-ALL (Eμ-ALL01) | Liver accumulation (non-targeted NPs). Spleen, lymph nodes, bone marrow accumulation (targeted NPs) | Lower tumor growth/burden rate | Similar to the conventional group | Similar to the conventional CAR T-cell group | Well tolerated, safer |
| DMAP-EDCI-DMF + zinc(ii) phthalocyanine (ZnPc), (photosensitizer: PS): C5 (ref. 129) | Dasatinib (small-molecule-tyrosine kinase inhibitor) | DMAP-EDCI-DMF + (ZnPc), (photosensitizer: PS)–dasatinib: C4 (PDT), tail vein | Nude mice, CCRF-CEM | Tumor accumulation. Rapid clearance of C4 | Lower tumor growth/burden rate | ND | Enhanced Antileukemic efficacy compared to the free drug under light exposure | Well tolerated, safer |
| Copolymer mPEG-PTMC160 | Dexamethasone (Dex) 2.5–5 mg kg−1 i.p. | mPEG-PTMC-Dex 41 nm, 5 mg kg−1 i.v. | NSG mice, primary T-ALL | Broad distribution. Accumulation in the major organs. Circulate to sanctuary sites (BM and BBB) | ND | ND | Enhanced Antileukemic efficacy compared to the free drug | Well tolerated, safer |
| PEG-PLA (polymeric micelles (PMs))148 | DOX (doxorubicin) 3 mg kg−1 i.p. | DOX-PMs-NPMBP 3 mg kg−1 i.p. | BALB/C-nude mice, Nalm6, resistance Nalm6 (B-ALL cell line) | ND | Lower tumor growth/burden rate | ND | Enhanced Antileukemic efficacy compared to the free drug | Well tolerated, safer |
| DOX-PMs-NPMBP 1.5 mg kg−1 i.p. | NCG mice, Nalm6, resistance Nalm6 (B-ALL cell line) | ND | Lower tumor growth/burden rate | Increased lifespan | ||||
| PLGA111 | 6-Mercaptopurine (6 MP) 15.75 mg kg−1 oral | PLGA-6-MP 138.01 ± 0.39 nm 15.75 mg kg−1 oral | Female NPG, Jurkat T-ALL | ND | Lower tumor growth/burden rate | Increased lifespan | Enhanced Antileukemic efficacy compared to the free drug | Well tolerated, safer |
| DSPE-PEG-DT7 (peptide-modified lecithin nanoparticles): TLnp136 | Gamma-secretase inhibitors (GSIs) with dexamethasone (DEX): D&G-sol | DT7-DEX + GSI co-loaded lecithin nanoparticles (TLnp/D&G) 32.36 ± 2.15 nm DEX 30 mg kg−1, GSI 30 mg kg−1 i.v. | NSG, CEM | Tumor accumulation | Lower tumor growth/burden rate | Increased lifespan | Enhanced Antileukemic efficacy compared to the free drug | Well tolerated, safer |
a
ND: not determined.