Neutrophil hitchhiking for drug delivery to the bone marrow

Luo, Zhenyu; Lu, Yichao; Shi, Yingying; Jiang, Mengshi; Shan, Xinyu; Li, Xiang; Zhang, Junlei; Qin, Bing; Liu, Xu; Guo, Xuemeng; Huang, Jiaxin; Liu, Yu; Wang, Sijie; Li, Qingpo; Luo, Lihua; You, Jian

doi:10.1038/s41565-023-01374-7

Cited by 62 publications

(20 citation statements)

References 37 publications

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“…This inflammatory chemotactic property entitles neutrophils with excellent ability to target postoperative tumor tissue. Similar to platelets, a neutrophil-based biomimetic drug delivery system also plays an important role in tumor-targeted treatment. ,, Hybrid membrane (PNM) derived from platelet and neutrophil membranes will inherit a variety of abilities of the source cells to obtain twindrive targeting for microenvironment regulation after surgery. Here, the ability of PNM to assist the accumulation of nanoparticles in damaged tumor tissue was demonstrated through in vivo fluorescent imaging guidance of IR820.…”

Section: Resultsmentioning

confidence: 99%

A Twindrive Precise Delivery System of Platelet-Neutrophil Hybrid Membrane Regulates Macrophage Combined with CD47 Blocking for Postoperative Immunotherapy

Sheng,

Jin,

Zhang

et al. 2024

ACS Nano

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During wound healing after cancer surgery, platelets, neutrophils, and macrophages accumulate at the wound site and induce important pathophysiological features. Utilizing these pathophysiological features, the development of targeted delivery systems for postoperative tumor immunotherapy is an important strategy. Herein, a twindrive precise delivery system of hybrid membrane combined with CD47 blocking is developed for targeted delivery and targeted regulation to induce postoperative immunotherapy. The precise delivery system consists of IR820-modified platelet-neutrophil hybrid membranes loaded with R848 nanoparticles. Based on the pathological characteristics of platelet aggregation and neutrophil tendency caused by the wound inflammatory microenvironment after tumor surgery, the twindrive delivery system could achieve targeted delivery and targeted regulation of immune drugs to tumor sites. After precise delivery guided by fluorescence imaging, R848 is targeted to reprogram M2 macrophages into M1 macrophages, stimulate dendritic cell maturation as an adjuvant, and then activate T cell immunity. R848 polarization and CD47 blockade together enhanced the phagocytosis function of macrophages, which combined with T cell-mediated cellular immune response to finally effectively inhibit postsurgical tumor recurrence, metastasis, and prolonged survival time. It develops a targeted delivery and regulatory system for cell-specific responses to the pathophysiological features of wound healing for postoperative immunotherapy.

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Section: Resultsmentioning

confidence: 99%

A Twindrive Precise Delivery System of Platelet-Neutrophil Hybrid Membrane Regulates Macrophage Combined with CD47 Blocking for Postoperative Immunotherapy

Sheng,

Jin,

Zhang

et al. 2024

ACS Nano

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“…A variety of polymeric micelles and liposome formulations have been used to this end. 10,43 We chose BSA to encapsulate DOX because BSA exhibits satisfactory biocompatibility and drug-loading capacity. 44 We are aware that doxorubicin is not currently used for clinical treatment of pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

Irreversible Electroporation-Induced Inflammation Facilitates Neutrophil-Mediated Drug Delivery to Enhance Pancreatic Cancer Therapy

Huang,

Wen,

Liang

et al. 2024

Mol. Pharmaceutics

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Pancreatic cancer is a deadly disease with a five-year overall survival rate of around 11%. Chemotherapy is a cornerstone in the treatment of this malignancy, but the intratumoral delivery of chemotherapy drugs is impaired by the highly fibrotic tumor-associated stroma. Irreversible electroporation (IRE) is an ablative technique for treating locally advanced pancreatic cancer. During a typical IRE procedure, high-intensity electric pulses are released to kill tumor cells through the irreversible disruption of the cytoplasm membranes. IRE also induces rapid tumor infiltration by neutrophils and offers an opportunity for neutrophil-mediated drug delivery. We herein showed that the IRE-induced neutrophil trafficking was facilitated by the upregulation of neutrophil chemotaxis and migration as well as the release of several chemoattractants. Doxorubicin-loaded bovine serum albumin nanoparticles were prepared and loaded into neutrophils at a ratio of 9.9 ± 1.2 to 11.7 ± 2.0 pg of doxorubicin per cell. The resultant formulation (NP@NEs) efficiently accumulated in the IRE-treated KPC-A377 murine pancreatic tumors with an uptake value of 10.7 ± 1.5 (percent of injected dose per gram of tissue, abbreviated as %ID/g) at 48 h after intravenous injection. In both Panc02 and KPC-A377 murine pancreatic tumor models, the combination of IRE + NP@NEs inhibited tumor growth more effectively than either monotherapy. The tumors treated with the combination also exhibited the lowest frequency of Ki67 + proliferating cells and the highest abundance of terminal deoxynucleotidyl transferase dUTP nick end labeling + (TUNEL + ) apoptotic cells among the experiment groups. Minimal treatment-associated toxicity was observed. Our findings suggest that neutrophil-mediated delivery of chemotherapy drugs is a useful tool to enhance the response of pancreatic cancer to IRE.

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“…Tang et al developed an M2-like macrophage-targeting NO-responsive nanoprobe and demonstrated the migration and critical role of M2-like macrophages in early tumor metastasis, suggesting the potential of targeting M2-like macrophages for enhanced drug accumulation in metastatic tumors . Moreover, other biological barriers such as the blood-brain barrier (BBB) and bone marrow-blood barrier also greatly restrict the access of nanomedicines to these targeted tissues, leading to low delivery efficiency.…”

Section: Tumor Abnormality-oriented Nanomedicine Design Overcoming De...mentioning

confidence: 99%

Tumor Abnormality-Oriented Nanomedicine Design

Zhou,

Xiang,

Qiu

et al. 2023

Chem. Rev.

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Anticancer nanomedicines have been proven effective in mitigating the side effects of chemotherapeutic drugs. However, challenges remain in augmenting their therapeutic efficacy. Nanomedicines responsive to the pathological abnormalities in the tumor microenvironment (TME) are expected to overcome the biological limitations of conventional nanomedicines, enhance the therapeutic efficacies, and further reduce the side effects. This Review aims to quantitate the various pathological abnormalities in the TME, which may serve as unique endogenous stimuli for the design of stimuli-responsive nanomedicines, and to provide a broad and objective perspective on the current understanding of stimuli-responsive nanomedicines for cancer treatment. We dissect the typical transport process and barriers of cancer drug delivery, highlight the key design principles of stimuli-responsive nanomedicines designed to tackle the series of barriers in the typical drug delivery process, and discuss the “all-into-one” and “one-for-all” strategies for integrating the needed properties for nanomedicines. Ultimately, we provide insight into the challenges and future perspectives toward the clinical translation of stimuli-responsive nanomedicines.

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Neutrophil hitchhiking for drug delivery to the bone marrow

Cited by 62 publications

References 37 publications

A Twindrive Precise Delivery System of Platelet-Neutrophil Hybrid Membrane Regulates Macrophage Combined with CD47 Blocking for Postoperative Immunotherapy

A Twindrive Precise Delivery System of Platelet-Neutrophil Hybrid Membrane Regulates Macrophage Combined with CD47 Blocking for Postoperative Immunotherapy

Irreversible Electroporation-Induced Inflammation Facilitates Neutrophil-Mediated Drug Delivery to Enhance Pancreatic Cancer Therapy

Tumor Abnormality-Oriented Nanomedicine Design

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