Calcium Orthophosphate in Liposomes for Co-Delivery of Doxorubicin Hydrochloride/Paclitaxel in Breast Cancer

Nanoparticles(NPs) show great advantages in cancer treatment byenabling controlled and targeted delivery of payloads to tumor sitesthrough the enhanced permeability and retention (EPR) effect. In thisstudy, highly effective pH-responsive and biodegradable calcium orthophosphate@liposomes(CaP@Lip) NPs with a diameter of 110 & PLUSMN; 20 nm were designed andfabricated. CaP@Lip NPs loaded with hydrophobic paclitaxel and hydrophilicdoxorubicin hydrochloride achieved excellent drug loading efficienciesof 70 and 90%, respectively. Under physiological conditions, the obtainedNPs are negatively charged. However, they switched to positively chargedwhen exposed to weak acidic environments by which internalizationcan be promoted. Furthermore, the CaP@Lip NPs exhibit an obvious structuralcollapse under acid conditions (pH 5.5), which confirms their excellentbiodegradability. The "proton expansion" effect in endosomesand the pH-responsiveness of the NPs facilitate the release of encapsulateddrugs from individual channels. The effectiveness and safety of thedrug delivery systems were demonstrated through in vitro and in vivoexperiments, with a 76% inhibition of tumor growth. These findingshighlight the high targeting ability of the drug-loaded NPs to tumorsites through the EPR effect, effectively suppressing tumor growthand metastasis. By combining CaP NPs and liposomes, this study notonly resolves the toxicity of CaP but also enhances the stabilityof liposomes. The CaP@Lip NPs developed in this study have significantimplications for biomedical applications and inspire the developmentof intelligent and smart drug nanocarriers and release systems forclinical use.