Immunotherapeutic interventions represent a promising approach to treating cancer, with strategies such as immune checkpoint blockade (ICB), immunogenic sonodynamic therapy (SDT), and immune adjuvant T cell delivery having exhibited clinical promise. In this report, we describe the use of cancer cell membrane-coated triphenylphosphonium (TPP) decorated nano-metal–organic framework (nMOF) constructs [Zr-TCPP(TPP)/R837@M] that were used to generate homologous, mitochondria-targeted platforms with a high rate of sonosensitizer loading. This construct was utilized to simultaneously promote tumor antigen presentation via enhancing SDT while synergistically promoting dendritic cell (DC) maturation through the delivery of the Toll-like receptor agonist R837. In vitro, these functionalized nMOFs were readily internalized by homologous tumor cells in which they were efficiently targeted to the mitochondria, promoting DC activation through the induction of immunogenic cell death (ICD) following ultrasound exposure. Moreover, this nanoplatform was able to achieve in vivo synergy with anti-CTLA-4 ICB to reverse immunosuppression tumor microenvironment (TME), thus achieving more robust antitumor efficacy capable of suppressing metastatic disease progression and facilitating the development of durable antitumor memory responses. Together, these results highlight a promising approach to achieving enhanced SDT activity while overcoming an immunosuppressive TME, thereby achieving more robust antitumor immunity.

Sonodynamic therapy (SDT), which uses reactive oxygen species to target tumors, has shown promise in the management of unresectable cancers. However, the hypoxic tumor environment limits SDT efficiency, making complete tumor destruction challenging. Here, a dual-sonosensitizer nanoplatform is developed by loading an alkyl radical generator (2,2-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride, AIPH) onto a zirconium metal-organic framework (Zr-MOF). The Zr-MOF@AIPH nanoparticles (NPs) can produce singlet oxygen, which can kill tumor cells under normoxic conditions, as well as alkyl radicals, which can kill tumor cells under both normoxic and hypoxic conditions. The combination of these free radicals further enhances SDT efficiency. Meanwhile, the nitrogen generated owing to AIPH decomposition can reduce the cavitation threshold and enhance the acoustic cavitation effect, thereby promoting NP penetration at the tumor site. Moreover, Zr-MOF@AIPH NPs exhibit good photoacoustic, fluorescence, and ultrasound imaging abilities due to their porphyrin-based structure and the nitrogen generated, which can remotely control NP delivery and determine the optimal therapeutic time window, ensuring the maximization of SDT efficiency. In vitro and in vivo examinations prove the superior antitumor efficacy, excellent biocompatibility, and favorable imaging ability of Zr-

The activation and functionalization of C-F bonds under mild conditions can serve as an important tool for organic syntheses including the modification of pharmaceuticals or agrochemicals and the synthesis of...

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Active tumor penetration has been recently recognized as a promising strategy to resolve the limitation of nanomedicine in terms of tumor penetration, but it is challenging to develop active transporting nanocarriers. Here, an ultrasonic cavitation‐assisted and acid‐activatable active transporting liposome for a broad range of tumors is reported. The active transporting liposome (size and charge dual‐conversional gemcitabine prodrug‐integrated liposomal nanodroplet (SCGLN)) overcomes the tight blood vessel walls with the aid of ultrasonic cavitation. The SCGLN subsequently transforms from micro‐size to nano‐size under prolonged ultrasound radiation. Once in the acidic tumor microenvironment, the nanosized SCGLN undergoes negative‐to‐positive charge‐reversal and triggers the cationization‐initiated transcytosis to penetrate deep into tumor parenchyma. The gemcitabine‐loaded SCGLN exhibits potent antitumor activity in multiple poorly permeable tumor models, which completely erases subcutaneous U251 glioma and stops the progression of orthotopic BxPC3 pancreatic ductal adenocarcinoma. This study presents a promising and universal strategy to develop active penetrating nanomedicines for efficient drug delivery in the low permeable tumor.