Intravesical chemotherapy synergize with an immune adjuvant by a thermo-sensitive hydrogel system for bladder cancer

Surgical resection remains the prefer option for bladder cancer treatment. However, the effectiveness of surgery is usually limited for the high recurrence rate and poor prognosis. Consequently, intravesical chemotherapy synergize with immunotherapy in situ is an attractive way to improve therapeutic effect. Herein, a combined strategy based on thermo-sensitive PLEL hydrogel drug delivery system was developed. GEM loaded PLEL hydrogel was intravesical instilled to kill tumor cells directly, then PLEL hydrogel incorporated with CpG was injected into both groins subcutaneously to promote immune responses synergize with GEM. The results demonstrated that drug loaded PLEL hydrogel had a sol-gel phase transition behavior in response to physiological temperature and presented sustained drug release, and the PLEL-assisted combination therapy could have better tumor suppression effect and stronger immunostimulating effect in vivo. Hence, this combined treatment with PLEL hydrogel system has great potential and suggests a clinically-relevant and valuable option for bladder cancer. A combined strategy based on thermo-sensitive PLEL hydrogel drug delivery system for bladder cancer was developed. GEM loaded PLEL hydrogel was intravesical instilled firstly, then PLEL hydrogel incorporated with CpG was injected into both groins subcutaneously to promote immune responses. Results demonstrated that drug loaded PLEL hydrogel had a sol-gel phase transition behavior and presented sustained drug release, and the PLEL-assisted combination therapy could have better tumor suppression effect and stronger immunostimulating effect in vivo. [Display omitted] •The triblock polymer PDLLA-PEG-PDLLA (PLEL) is a thermos-sensitive hydrogel for localized drug delivery.•Drug loaded PLEL hydrogel achieves the sustained release of drug and extend retention time of Gemcitabine in bladder.•Intravesical chemotherapy with immunothrapy by thermo-sensitive PLEL system improves anti-tumor effect for bladder cancer.•Combined therapy strategy assisted by PLEL hydrogel promote related immune response to help kill bladder cancer cells.