MSCs-engineered biomimetic PMAA nanomedicines for multiple bioimaging-guided and photothermal-enhanced radiotherapy of NSCLC.

BACKGROUND: The recently developed biomimetic strategy is one of the mostly effective strategies for improving the theranostic efficacy of diverse nanomedicines, because nanoparticles coated with cell membranes can disguise as "self", evade the surveillance of the immune system, and accumulate to the tumor sites actively. RESULTS: Herein, we utilized mesenchymal stem cell memabranes (MSCs) to coat polymethacrylic acid (PMAA) nanoparticles loaded with Fe(III) and cypate-an derivative of indocyanine green to fabricate Cyp-PMAA-Fe@MSCs, which featured high stability, desirable tumor-accumulation and intriguing photothermal conversion efficiency both in vitro and in vivo for the treatment of lung cancer. After intravenous administration of Cyp-PMAA-Fe@MSCs and Cyp-PMAA-Fe@RBCs (RBCs, red blood cell membranes) separately into tumor-bearing mice, the fluorescence signal in the MSCs group was 21% stronger than that in the RBCs group at the tumor sites in an in vivo fluorescence imaging system. Correspondingly, the T1-weighted magnetic resonance imaging (MRI) signal at the tumor site decreased 30% after intravenous injection of Cyp-PMAA-Fe@MSCs. Importantly, the constructed Cyp-PMAA-Fe@MSCs exhibited strong photothermal hyperthermia effect both in vitro and in vivo when exposed to 808 nm laser irradiation, thus it could be used for photothermal therapy. Furthermore, tumors on mice treated with phototermal therapy and radiotherapy shrank 32% more than those treated with only radiotherapy. CONCLUSIONS: These results proved that Cyp-PMAA-Fe@MSCs could realize fluorescence/MRI bimodal imaging, while be used in phototermal-therapy-enhanced radiotherapy, providing desirable nanoplatforms for tumor diagnosis and precise treatment of non-small cell lung cancer.

Combined Doxorubicin Mesoporous Carbon Nanospheres for Effective Tumor Lymphatic Metastasis by Multi-Modal Chemo-Photothermal Treatment in vivo.

Introduction: Sentinel lymph node (SLN) is the first regional lymph node where tumor cells metastasize, and its identification and treatment are of great significance for the prevention of tumor metastasis. However, the current clinical modalities for identification and treatment of SLN are still far from satisfactory owing to their high cost, invasiveness and low accuracy. We aim to design a novel nanomedicine system for SLN imaging and treatment with high efficacy. Methods: We designed and prepared hollow mesoporous carbon spheres (HMCS) and loaded with the chemotherapeutic drug doxorubicin (DOX), which is then modified with polyvinyl pyrrolidone (PVP) to obtain nanomedicine: HMCS-PVP-DOX. Results: HMCS-PVP with a size of about 150 nm could retain in the lymph nodes for a long time and stain the lymph nodes, which could be easily observed by the naked eye. At the same time, HMCS-PVP exhibited excellent photoacoustic and photothermal imaging capabilities, realizing multimodal imaging to locate lymph nodes precisely. Due to its high specific surface area, HMCS could be largely loaded with the chemotherapeutic drug doxorubicin (DOX). HMCS-PVP-DOX displayed highly efficient synergistic chemotherapy-photothermal therapy for lymphatic metastases in both cellular and animal experiments due to its significant photothermal effect under 1064 nm laser irradiation. HMCS-PVP-DOX also displayed great stability and biosafety. Discussion: Multifunctional nanomedicine HMCS-PVP-DOX is expected to provide a novel paradigm for designing nanomedicine to the diagnosis and treatment of lymphatic metastases because of its good stability and safety.

Oxygen-evolving photosynthetic cyanobacteria for 2D bismuthene radiosensitizer-enhanced cancer radiotherapy.

The local hypoxic tumor environment substantially hampers the therapeutic efficiency of radiotherapy, which typically requires the large X-ray doses for tumor treatment but induces the serious side effects. Herein, a biomimetic radiosensitized platform based on a natural in-situ oxygen-evolving photosynthetic cyanobacteria combined with two-dimensional (2D) bismuthene with high atomic-number (Z) components, is designed and engineered to effectively modulate the radiotherapy-resistant hypoxic tumor environment and achieve sufficient radiation energy deposition into tumor. Upon the exogenous sequential irradiation of 660 nm laser and X-ray beam, continuous photosynthetic oxygen evolution by the cyanobacteria and considerable generation of reactive oxygen species by the 2D bismuthene radiosensitizer substantially augmented the therapeutic efficacy of radiotherapy and suppressed the in vivo tumor growth, as demonstrated on both LLC-lung tumor xenograft-bearing C57/B6 mice model and 4T1-breast tumor xenograft-bearing Balb/c mice model, further demonstrating the photosynthetic hypoxia-alleviation capability and radiosensitization performance of the engineered biomimetic radiosensitized platform. This work exemplifies a distinct paradigm on the construction of microorganism-enabled tumor-microenvironment modulation and nanoradiosensitizer-augmented radiotherapy for efficient tumor treatment.

Photothermal/nitric oxide synergistic anti-tumour therapy based on MOF-derived carbon composite nanoparticles.

Conventional organic photothermal conversion reagents still face some challenges for their real applications, such as the requirement of carriers for in vivo transport, uncontrolled degradation during use, reduction in photothermal conversion efficiency by repeated exposure to a near-infrared laser, and so on. Herein, uniform ZIF-8 nanoparticles were prepared first, and then carbonized and etched to form porous carbon nanoparticles (CNPs). After loading an NO donor and wrapping with red blood cell membrane, the novel CNP-NO@RBC photothermal agent integrated with in situ imaging ability was obtained. Due to the great photothermal conversion efficiency of the carbon material and the specific release of NO from the loaded NO conformer, the CNP-NO@RBCs show excellent tumour cell killing ability based on light-triggered photothermal/gas therapy at lower doses of CNP-NO@RBCs.

Patterns of Failure in Patients With Advanced Non-Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitors.

OBJECTIVE: The advent of immune checkpoint inhibitors (ICIs) has rapidly transformed the treatment paradigm of non-small cell lung cancer (NSCLC). Despite the durability of response to ICIs, the vast majority of patients will later develop progression. However, the failure patterns of ICI treatment are unknown. Here, our study explored the failure patterns in advanced NSCLC patients treated with ICIs. METHODS: A cohort of 156 IIIB or IV NSCLC patients treated with first-/second-line ICIs were retrospectively analyzed. Patients who experienced clinical benefit and then developed progression were identified. The disease progression patterns were divided into three categories: progression in new sites, progression in existing sites, and combined progression. The number of progression sites was also recorded. RESULTS: Before the cutoff date, 91 (77.1%) patients had experienced disease progression; 34% of patients had progressed in the last 9 months of the first year. Fifty-three (58.2%) patients had developed progression at existing lesions, and 56 (61.5%) patients had shown ≤2 progression sites (oligo-progression). In patients with oligo-progression, the median time of disease progression was 8.23 months and the counterpart (systemic progression) was 5.97 months. The oligo-progression patients showed prolonged median overall survival (27.23 months) compared with patients with systemic progression (18.87 months). CONCLUSIONS: Failure patterns of ICI therapy were predominantly "existing" sites, and the most common lesions of progression were the lung and lymph nodes. Most patients experienced oligo-progression which occurred later than systemic progression and showed prolonged overall survival. The control of the local lesions might be beneficial to improve ICI treatment efficacy.

Red-blood-cell-membrane-enveloped magnetic nanoclusters as a biomimetic theranostic nanoplatform for bimodal imaging-guided cancer photothermal therapy.

The use of red blood cell (RBC) membrane coatings has recently been found to be a biomimetic strategy to confer inner core nanomaterials with improved pharmacokinetic profiles by utilizing the intrinsic long blood circulation time of RBCs. Here, we envelope superparamagnetic nanoclusters (MNCs) with RBC membrane ghosts to obtain MNC@RBCs with significantly improved physiological stability compared to that of bare MNCs. After being loaded with near-infrared (NIR) cypate molecules, the as-prepared Cyp-MNC@RBCs show remarkably increased NIR absorbance and resultant efficient photothermal conversion efficacy. By tracking the NIR fluorescence of cypate in an in vivo fluorescence imaging system, we uncover that such Cyp-MNC@RBCs upon intravenous injection show significantly improved tumor-homing capacity as compared to bare cypate-loaded MNCs. A similar result is further evidenced by recording the T2-weighted magnetic resonance imaging (MRI) signal of MNCs. Furthermore, upon exposure to 808 nm laser irradiation, the tumors grown on the mice with the intravenous injection of Cyp-MNC@RBCs show a higher temperature increase than the tumors grown on the mice injected with plain MNC@RBCs and thus are significantly suppressed via photothermal ablation. This study presents the preparation of biomimetic Cyp-MNC@RBCs with greatly improved tumor-homing capacity as multifunctional nanotheranostic agents for fluorescence and MRI bimodal imaging-guided cancer photothermal therapy.