A nanoliposome-based photoactivable drug delivery system for enhanced cancer therapy and overcoming treatment resistance

Recently, stimuli-responsive drug delivery systems (DDSs) with high spatial/temporal resolution bring many benefits to cancer treatment. However, cancer cells always develop ways to resist and evade treatment, ultimately limit the treatment efficacy of the DDSs. Here, we introduce photo-activated nanoliposomes (PNLs) that impart light-induced cytotoxicity and reversal of drug resistance in synchrony with a photoinitiated and rapid release of antitumor drug. The PNLs consist of a nanoliposome doped with a photosensitizer (hematoporphyrin monomethyl ether [HMME]) in the lipid bilayer and an antitumor drug doxorubicin (DOX) encapsulated inside. PNLs have several distinctive capabilities: 1) carrying high loadings of DOX and HMME and releasing the payloads in a photo-cleavage manner with high spatial/temporal resolution at the site of actions via photocatalysis; 2) reducing drug efflux in MCF-7/multidrug resistance cells via decreasing the level of P-glycoprotein induced by photodynamic therapy (PDT); 3) accumulating in tumor site taking advantage of the enhanced permeability and retention effect; and 4) combining effective chemotherapy and PDT to exert much enhanced anticancer effect and achieving significant tumor regression in a drug-resistant tumor model with little side effects.