A combination strategy of DOX and VEGFR-2 targeted inhibitor based on nanomicelle for enhancing lymphoma therapy

Lymphoma is a hematological malignancy with an increasing mortality rate. Nevertheless, the treatment strategy against lymphoma remains limited. Doxorubicin (DOX) is a broad-spectrum anti-tumor chemotherapeutic drug, the clinical application of which is limited by serious adverse effects and drug resistance. In this work, biodegradable methoxy poly(ethylene glycol)-block-poly(lactic acid) (mPEG-PLA) nanomicelles co-delivering of DOX and apatinib (AP) (DOX-AP/m) was developed for lymphoma therapy. The average particle size of the self-assembled drug-loaded nano-micelle was 31.94 nm. It is revealed that AP can enhance the uptake of DOX by tumor cells. The in vivo and in vitro experimental results revealed that DOX-AP/m combination therapy could inhibit proliferation and promote apoptosis of lymphoma cells, and greatly suppress tumor growth. Our study indicated that DOX-AP/m might provide new insight and hold great potential in the treatment of lymphoma. The DOX-AP/m was prepared by self-assembly of mPEG-PLA polymers, anthracycline antibiotic doxorubicin (DOX) and anti-VEGFR-2 apatinib (AP). AP significantly enhanced the cellular uptake and improved the therapeutic efficacy of DOX. DOX-AP/m is powerful in inhibiting proliferation and promoting apoptosis of lymphoma cells, and greatly suppressing tumor growth, which might provide new insight and holds great potential in the treatment of lymphoma. [Display omitted]