Immunotherapeutic hydrogel for co-delivery of STAT3 siRNA liposomes and lidocaine hydrochloride for postoperative comprehensive management of NSCLC in a single application

Despite standard treatment for non-small cell lung cancer(NSCLC)being surgical resection,cancer recurrence and complications,such as induction of malignant pleural effusion(MPE)and significant postoperative pain,usually result in treatment failure.In this study,an alginate-based hybrid hydrogel(SOG)is developed that can be injected into the resection surface of the lungs during surgery.Briefly,endoplasmic reticulum-modified liposomes(MSLs)pre-loaded with the signal transducer and activator of transcription 3(STAT3)small interfering RNA and lidocaine hydrochloride are encapsulated in SOG.Once applied,MSLs strongly downregulated STAT3 expression in the tumor microenvironment,resulting in the apoptosis of lung cancer cells and polarization of tumor-associated macrophages towards the M1-like phenotype.Meanwhile,the release of lidocaine hydrochloride(LID)was beneficial for pain relief and natural killer cell activation.Our data demonstrated MSL@LID@SOG not only efficiently inhibited tumor growth but also potently improved the quality of life,including reduced MPE volume and pain relief in orthotopic NSCLC mouse models,even with a single administration.MSL@LID@SOG shows potential for comprehensive clinical management upon tumor resection in NSCLC,and may alter the treatment paradigms for other cancers.

Precise design strategies of nanomedicine for improving cancer therapeutic efficacy using subcellular targeting

Therapeutic efficacy against cancer relies heavily on the ability of the therapeutic agents to reach their final targets.The optimal targets of most cancer therapeutic agents are usually biological macromolecules at the subcellular level,which play a key role in carcinogenesis.Therefore,to improve the therapeutic efficiency of drugs,researchers need to focus on delivering not only the therapeutic agents to the target tissues and cells but also the drugs to the relevant subcellular structures.In this review,we discuss the most recent construction strategies and release patterns of various cancer cell subcellular-targeting nanoformulations,aiming at providing guidance in the overall design of precise nanomedicine.Additionally,future challenges and potential perspectives are illustrated in the hope of enhancing anticancer efficacy and accelerating the translational progress of precise nanomedicine.