Self-targeted hyaluronic acid-b-poly (β-amino ester) pH-switchable polymersome for guided doxorubicin delivery to metastatic breast cancer

In this study, a targeted pH-sensitive polymersome incorporating doxorubicin (DOX) was manufactured implementing diblock copolymer of hyaluronic acid-b-pPoly (β-amino ester) (HA-PBAE). The hydrophilic DOX was loaded into the aqueous compartment of HA-PBAE polymersomal structure during nanoprecipitation process with 60 % ± 3.0 entrapment efficiency (EE%) and 5.3 % ± 0.2 loading content (LC%) while demonstrating spherical morphology with size of 196 ± 3.8 nm and PDI of 0.3. The prepared platform (DOX-HA-PBAE) illustrated accelerated DOX release in acidic pH 5.4, and showed significantly higher cytotoxicity and cellular internalization in comparison with free DOX against 4T1 cell line (CD44 positive cell). In contrast, no significant growth inhibition was observed in CHO cell line (CD44 negative cell). Furthermore, DOX-HA-PBAE platform displayed higher therapeutic efficacy, favorable tumor accumulation and lower systemic toxicity in comparison with free DOX based on obtained experimental data in ectopic 4T1 tumor model in BALB/c Female mice in terms of tumor growth rate, survival rate, body weight loss, ex vivo biodistribution and pathological evaluations. The obtained results demonstrated that DOX-HA-PBAE polymersomes have potential to be used in metastatic breast cancer therapy with promising characteristics in terms of tumor growth suppression and safety profile.