Sonodynamic therapy (SDT) is a noninvasive ultrasound-triggered therapeutic strategy for site-specific treatment of tumors with great depth penetration. The design of nano-sonosensitizers suitable for SDT treatment of bladder cancer (BCa) post-intravesical instillation has not yet been reported. Herein, a transmucosal oxygen-self-production SDT nanoplatform is developed to achieve highly efficient SDT against BCa. In this system, fluorinated chitosan (FCS) is synthesized as a highly effective nontoxic transmucosal delivery carrier to assemble with meso-tetra(4-carboxyphenyl)porphineconjugated catalase (CAT-TCPP). The formed CAT-TCPP/ FCS nanoparticles after intravesical instillation into the bladder cavity exhibit excellent transmucosal and intratumoral penetration capacities and could efficiently relieve hypoxia in tumor tissues by the catalase-catalyzed O 2 generation from tumor endogenous H 2 O 2 to further improve the therapeutic efficacy of SDT to ablate orthotopic bladder tumors under ultrasound. Our work presents a nano-sonosensitizer formulation with FCS to enhance transmucosal delivery and intratumoral diffusion and CAT to improve tumor oxygenation, promising for instillation-based SDT to treat bladder tumors without the concern of systemic toxicity.

Currently, there is a huge demand to develop chemoimmunotherapy with reduced systemic toxicity and potent efficacy to combat late-stage cancers with spreading metastases. Here, we report several “cocktail” therapeutic formulations by mixing immunogenic cell death (ICD)–inducing chemotherapeutics and immune adjuvants together with alginate (ALG) for localized chemoimmunotherapy. Immune checkpoint blockade (ICB) antibody may be either included into this cocktail for local injection or used via conventional intravenous injection. After injection of such cocktail into a solid tumor, in-situ gelation of ALG would lead to local retention and sustained release of therapeutics to reduce systemic toxicity. The chemotherapy-induced ICD with the help of immune adjuvant would trigger tumor-specific immune responses, which are further amplified by ICB to elicit potent systemic antitumor immune responses in destructing local tumors, eliminating metastases and inhibiting cancer recurrence. Our strategy of combining clinically used agents for tumor-localized cocktail chemoimmunotherapy possesses great potential for clinical translation.

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By inducing tumor-specific immune responses, tumor vaccines have recently aroused great research interest. Herein, we design a targeted nanovaccine by equipping cell membrane vesicles (CMVs) harvested from tumor cells with functional DNA including CpG oligonucleotide, an agonist for toll-like receptor 9, as well as an aptamer targeting the dendritic cell (DC)-specific intercellular adhesion molecule (ICAM)-3 grabbing nonintegrin (DC-SIGN) receptor overexpressed on DCs. Such DNA-modified CMVs could target DCs and further stimulate their maturation. Notably, our nanovaccines could trigger robust antitumor immune responses to effective delay the tumor growth. Moreover, the combination of CMV-based nanovaccines with an immune checkpoint blockade could result in improved therapeutic responses by eliminating the majority of the tumors as well as long-term immune memory to prevent tumor recurrence. Therefore, by simply assembling functional DNA on CMVs harvested from tumor cells, we propose a general platform of DC-targeted personalized cancer vaccines for effective and specific cancer immunotherapy.

Hyperthermia induced by the alternating magnetic field (AMF) to heat magnetic nanomaterials localized within the tumor has attracted wide attention due to its ability in effective tumor ablation, low side effects, and deep tissue penetration. However, rather strong AMFs are often needed to realize effective magnetic hyperthermia of tumors. Herein, it is discovered that nonmagnetic gallium–indium liquid metal (GaIn LM) above certain sizes prepared by the shearing force could be effectively heated up under AMF with a low field intensity owing to the eddy‐thermal effect, which could be utilized for AMF‐induced hyperthermia treatment of tumors. As demonstrated in experiments using mice bearing subcutaneous 4T1 breast tumors and rats with deeply seated orthotopic liver tumors, local injection of GaIn LM followed by AMF treatment could result in effective ablation of those tumors. With great in vitro biocompatibility, such GaIn LM also shows no appreciable in vivo toxicity to mice within two months. This work thus presents a new type of thermal ablation therapy using nonmagnetic, biocompatible, and injectable LM to ablate tumors under a low‐field‐intensity AMF, with the eddy‐thermal heating mechanism distinctive from that in conventional magnetic hyperthermia therapies using magnetic nanoagents.