A pH-sensitive liposome formulation of a peptidomimetic-Dox conjugate for targeting HER2 + cancer

• A pH-sensitive liposome containing peptidomimetic-doxorubicin conjugate was developed. • The formulation was able to release more the drug conjugate at pH 6.5 comapred to 7.4. • The cellular uptake of the conjugate was high in HER2 positive cancer cells. • The formulation exhibited anticancer activity in 3D tumor spheroid model. • The formulation was able to suppress the NSCLC tumor in mice model. Cancer treatment faces the challenge of selective delivery of the cytotoxic drug to the desired site of action to minimize undesired side effects. The liposomal formulation containing targeting ligand conjugated cytotoxic drug can be an effective approach to specifically deliver chemotherapeutic drugs to cancer cells that overexpress a particular cell surface receptor. This research focuses on the in vitro and in vivo studies of a peptidomimetic ligand attached doxorubicin for the HER2 positive lung and breast cancer cells transported by a pH-dependent liposomal formulation system for the enhancement of targeted anticancer treatment. The selected pH-sensitive liposome formulation showed effective pH-dependent delivery of peptidomimetic-doxorubicin conjugate at lower pH conditions mimicking tumor microenvironment (pH-6.5) compared to normal physiological conditions (pH 7.4), leading to the improvement of cell uptake. In vivo results revealed the site-specific delivery of the formulation and enhanced antitumor activity with reduced toxicity compared to the free doxorubicin (Free Dox). The results suggested that the targeting ligand conjugated cytotoxic drug with the pH-sensitive liposomal formulation is a promising approach to chemotherapy.