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

Abstract

Nanoparticles (NPs) show great advantages in cancer treatment by enabling controlled and targeted delivery of payloads to tumor sites through the enhanced permeability and retention (EPR) effect. In this study, highly effective pH-responsive and biodegradable calcium orthophosphate@liposomes (CaP@Lip) NPs with a diameter of 110 ± 20 nm were designed and fabricated. CaP@Lip NPs loaded with hydrophobic paclitaxel and hydrophilic doxorubicin hydrochloride achieved excellent drug loading efficiencies of 70 and 90%, respectively. Under physiological conditions, the obtained NPs are negatively charged. However, they switched to positively charged when exposed to weak acidic environments by which internalization can be promoted. Furthermore, the CaP@Lip NPs exhibit an obvious structural collapse under acid conditions (pH 5.5), which confirms their excellent biodegradability. The "proton expansion" effect in endosomes and the pH-responsiveness of the NPs facilitate the release of encapsulated drugs from individual channels. The effectiveness and safety of the drug delivery systems were demonstrated through in vitro and in vivo experiments, with a 76% inhibition of tumor growth. These findings highlight the high targeting ability of the drugloaded NPs to tumor sites through the EPR effect, effectively suppressing tumor growth and metastasis. By combining CaP NPs and liposomes, this study not only resolves the toxicity of CaP but also enhances the stability of liposomes. The CaP@Lip NPs developed in this study have significant implications for biomedical applications and inspire the development of intelligent and smart drug nanocarriers and release systems for clinical use.

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“…At pH 5.5, nearly 63.33% of PTX was released within 48 h, while at pH 7.4, the 40.47% of the PTX was released. The slow release of PTX in NPs and the pH-responsive drug release minimize the adverse effects on healthy cells, making it beneficial for tumor treatment ( Chen et al, 2023 ).…”

“…NPs utilize the EPR effect to deliver drug molecules to the tumor site in a controlled and targeted manner, demonstrating significant advantages in cancer treatment. Chen et al (2023) prepared pH-responsive and biodegradable calcium orthophosphate@liposomes (CaP@Lip) NPs for loading hydrophobic PTX and hydrophilic doxorubicin (DOX) hydrochloride. Under physiological conditions, the obtained NPs carry a negative charge but they convert to a positive charge when exposed to a weakly acidic environment, thereby promoting drug internalization.…”