ArticleProceedings of the National Academy of Sciences of the United States of America2022
A single local delivery of paclitaxel and nucleic acids via an immunoactive polymer eliminates tumors and induces antitumor immunity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Fibrinogen-Drug Nanoparticles Achieve Durable Responses in Pancreatic and Breast Cancer Murine Models.ACS pharmacology & translational science · 2026Article
- Advances in Polyethyleneimine-Derived Nanoformulations.Small science · 2026Review
- Nanoparticulate Immunoactive Complex for Local Chemoimmunotherapy: From Murine Models to Pilot Canine Study.Cancer research communications · 2026Article
- Helper lipid-engineered extracellular vesicles enable PET imaging-guided pulmonary siRNA delivery to treat lung metastasis.Science advances · 2026Article
- Nanomaterial-Enabled Modulation of Tumor-Associated Macrophages and Dendritic Cells to Enhance Cancer Immunotherapy.Nanomaterials (Basel, Switzerland) · 2026Review
- Research Progress of Multicomponent Co-Loaded Nanomedicine Delivery Systems for Tumor Immunotherapy.International journal of nanomedicine · 2026Review
- Drug Delivery Systems Repurposing Taxanes as Antitumor Immune Modulators.Biomaterials research · 2026Review
- A sphingolipid-derived paclitaxel nanovesicle enhances efficacy of combination therapies in triple-negative breast cancer and pancreatic cancer.Nature cancer · 2025Article
- A sphingolipid-derived paclitaxel nanovesicle for improved cancer therapy.Nature cancer · 2025Article
- Optogenetic-Controlled iPSC-Based Vaccines for Prophylactic and Therapeutic Tumor Suppression in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Timely administration of drug combination improves chemoimmunotherapy of an immune-cold tumor.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Delivery of STING agonists for cancer immunotherapy.Current opinion in biotechnology · 2024Review
- One-step flow synthesis of size-controlled polymer nanogels in a fluorocarbon microfluidic chip.RSC advances · 2024Article
- Systemic Delivery of Paclitaxel by Find-Me Nanoparticles Activates Antitumor Immunity and Eliminates Tumors.ACS nano · 2024Article
- High-Dose Paclitaxel and its Combination with CSF1R Inhibitor in Polymeric Micelles for Chemoimmunotherapy of Triple Negative Breast Cancer.Nano today · 2023Article
- In Situ Vaccination with Mitochondria-Targeting Immunogenic Death Inducer Elicits CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Smart Polymeric Nanoparticles in Cancer Immunotherapy.Pharmaceutics · 2023Review
- Nanocarrier-Mediated Immunogenic Cell Death for Melanoma Treatment.International journal of nanomedicine · 2023Review
- Different Influences of Biotinylation and PEGylation on Cationic and Anionic Proteins for Spheroid Penetration and Intracellular Uptake to Cancer Cells.Journal of microbiology and biotechnology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Despite recent advances in cancer therapy, hard-to-reach, unidentified tumors remain a significant clinical challenge. A promising approach is to treat locatable and accessible tumors locally and stimulate antitumor immunity in situ to exert systemic effects against distant tumors. We hypothesize that a carrier of immunotherapeutics can play a critical role in activating antitumor immunity as an immunoadjuvant and a local retainer of drug combinations. Here, we develop a polyethyleneimine-lithocholic acid conjugate (2E′), which forms a hydrophobic core and cationic surface to codeliver hydrophobic small molecules and anionic nucleic acids and activates antigen-presenting cells via the intrinsic activities of 2E′ components. 2E′ delivers paclitaxel and small-interfering RNA (siRNA) targeting PD-L1 (or cyclic dinucleotide, [CDN]) to induce the immunogenic death of tumor cells and maintain the immunoactive tumor microenvironment, and further activates dendritic cells and macrophages, leveraging the activities of loaded drugs. A single local administration of 2E′ or its combination with paclitaxel and PD-L1–targeting siRNA or CDN induces strong antitumor immunity, resulting in immediate regression of large established tumors, tumor-free survival, an abscopal effect on distant tumors, and resistance to rechallenge and metastasis in multiple models of murine tumors, including CT26 colon carcinoma, B16F10 melanoma, and 4T1 breast cancer. This study supports the finding that local administration of immunotherapeutics, when accompanied by the rationally designed carrier, can effectively protect the host from distant and recurrent diseases.
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