Innovative in-situ forming composite hydrogel: pH-responsive nanogel and combretastatin A4 liposome for breast cancer therapy

Breast cancer, a malignant neoplasm prevalent among females, necessitates surgical intervention alongside adjuvant or neoadjuvant chemotherapy, which is fraught with severe side effects and elevated postoperative recurrence rates, contributing to increased mortality. This study presents an innovative composite hydrogel system integrating doxorubicin loaded pH-sensitive nanogels and combretastatin A4 loaded liposomes, aimed at achieving both antitumor efficacy and metastasis prevention. doxorubicin loaded pH sensitive nanogel particle size was 151.7 ± 3.25 nm, with negative surface charge. CA4 loaded liposomes with negatively charged and particle size 85.06 ± 1.7 nm was synthesized by thin film hydration technique. The doxorubicin and CA4 encapsulation efficiency were 98 ± 1.15 % and 87 ± 1.2 %, respectively. The hydrogel swelling index was measured for 45 minutes, which reached its highest value (25.86%) after 20 minutes. The amount of degradation of the hydrogel was also measured over 31 days and the percentage of degradation was reported as 10.41%. Our findings indicate that the CA4-loaded liposomes and doxorubicin loaded nanogel were effectively suppressed the proliferation of the 4T1 cell line and exhibited a synergistic effect when combined. Animal experiments were validated that the composite hydrogel significantly hinders tumor proliferation and extends survival compared to other treatment cohorts within 4T1 breast tumor bearing murine models. Collectively, this composite hydrogel represents a potentially effective strategy for breast cancer therapy and warrants further exploration.