No abstract

Photodynamic therapy (PDT) has shown the potential of triggering systemic antitumor immune responses. However, while the oxygen‐deficient hypoxic tumor microenvironment is a factor that limits the PDT efficacy, the immune responses after conventional PDT usually are not strong enough to eliminate metastatic tumors. Herein, a light‐triggered in situ gelation system containing photosensitizer‐modified catalase together with poly(ethylene glycol) double acrylate (PEGDA) as the polymeric matrix is designed. Immune adjuvant nanoparticles are further introduced into this system to trigger robust antitumor immune responses after PDT. Following local injection of the mixed precursor solution into tumors and the subsequent light exposure, polymerization of PEGDA can be initiated to induce in situ gelation. Such hybrid hydrogel with long‐term tumor retention of various agents and the ability to enable persistent tumor hypoxia relief can enable multiple rounds of PDT, which results in significantly enhanced immune responses by multiround stimulation. Further combination of such gel‐based multiround PDT with anticytotoxic T‐lymphocyte antigen‐4 checkpoint blockade offers not only the abscopal effect to inhibit growth of distant tumors but also effective long‐term immune memory protection from rechallenged tumors. Therefore, such a light‐triggered in situ gelation system by a single‐dose injection can enable greatly enhanced photoimmunotherapy by means of repeated stimulations.

Photoacoustic (PA) imaging based on the photon-to-ultrasound conversion allows the imaging of optical absorbers in deep tissues with high spatial resolution. However, the inherent optical absorbance of biomolecules (e.g., hemoglobin, melanin, etc.) would show up as tissue background signals to interfere with signals from the contrast agent during in vivo PA imaging, limiting the imaging sensitivity. Herein, an ultrasound (US)-responsive PA imaging probe based on microbubbles (MBs) containing gold nanoparticles (Au NPs) is designed for in vivo "background-free" PA imaging. The obtained Au@lip MBs with separated Au NPs decorated within the lipid shell of MBs show low PA signals under near-infrared (NIR) excitation. Interestingly, under exposure to US pulses, those Au@lip MBs would burst to form nanoscale aggregates of Au@lip NPs, which exhibit significantly enhanced NIR PA signals due to their red-shifted surface plasmon resonance. Therefore, by subtracting the PA image captured pre-US burst from that captured post-US burst, the tissue background PA signals could be deducted to enable background-free PA imaging with high sensitivities as demonstrated by multiple ex vivo and in vivo experiments. This work presents a simple yet effective strategy to deduct background signals during PA imaging, which is promising for accurate PA detection of targets in tissues with a strong background.

Vaccines are one of utmost important weapons in modern medicine to fight a wide range of diseases. To achieve optimal vaccination effects, repeated injections of vaccines are often required, which would largely decrease patient comfort. Herein, an ultrasound-responsive self-healing hydrogel system loaded with nanovaccines is designed for remotely controlled tumor vaccine release and individualized cancer immunotherapy. The gel could be transformed into sol status in response to ultrasound treatment, allowing a burst release of nanovaccines, and self-healed to gel afterward. For mice with a single subcutaneous injection of nanovaccine-loaded gel and multiple ultrasound treatments, repeatedly released nanovaccines could elicit antitumor immune responses, which in combination with immune checkpoint blockade could effectively inhibit established tumors, and prevent postoperative tumor metastases and recurrence based on our personalized nanovaccine system. This work presents an easy-to-operate strategy to realize controllable and durable delivery of vaccines against cancer and potentially other types of diseases.

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