A size shrinkable dendrimer-lipid hybrid nanoassembly for reversing tumor drug resistance

Drug resistance is a major obstacle in tumor therapy. One effective approach to overcoming this issue is by improving the penetration of drugs into the lesions. Here, we report size shrinkable dendrimer-lipid hybrid nanoassemblies (PATU-lipid-PEG/DOX). The PATU-lipid-PEG/DOX have initial sizes of ∼92 nm, which are ideal for blood circulation and tumor vascular penetration. Once PATU-lipid-PEG/DOX at tumor sites, they will disassemble and release small dendrimers (∼3 nm) to realize deep tumor penetration. As a result, Doxorubicin (DOX) can be delivered intracellularly, thereby reversing tumor multidrug resistance. The efficacy of PATU-lipid-PEG/DOX was validated in drug-resistant tumor mice. This study provides a versatile drug delivery platform to address the challenges of tumor drug resistance.