ArticleScience advances2025
Pulsatile sequential drug release system for cascade tumor deep penetration and differentiation therapy to enhance chemoimmunotherapy.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
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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
5 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Hypoxic cancer stem cell-immune niches in the tumor microenvironment: a Systematic Review of mechanisms and therapeutic implications.Frontiers in immunology · 2026Pooled it
- Senescent tumor cell membrane-based "time engine" nanosystem amplifies endoplasmic reticulum targeting for metastasis blockade.Science advances · 2026Article
- Mimetic Core-Sheath Silk Sutures with Superior-Strength for Pain Management, Anti-Infection and Wound Healing.Advanced healthcare materials · 2026Article
- pH-Responsive Materials for Therapy and Precision Biomedical Imaging.Chemical & biomedical imaging · 2026Review
- Bio-Polymers Based Functionalized Hydrogel Carriers for Targeted Oncology Therapies: Current Progress and Future Perspectives.International journal of nanomedicine · 2026Review
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer stem cells (CSCs) and myeloid-derived suppressor cells (MDSCs) contribute to chemoresistance and immunosuppression, constraining chemoimmunotherapy outcomes. Differentiation therapy, aiming to mature CSCs and MDSCs, shows great promise. However, its efficacy is hindered by limited accessibility in hypoxic deep tumor regions. Inspired by the apoptotic body (ApoBD)-mediated deep tumor penetration, we design a pulsatile sequential drug release system with a core-shell structure. The reversible acid-responsive shell protonates and swells in lysosomes to release doxorubicin, inducing lysosomal escape and cell apoptosis. In ApoBDs, it deprotonates and contracts to prevent excessive drug release. After deep penetration via ApoBDs, the hypoxia-responsive core releases all-trans retinoic acid to reverse CSCs and MDSCs, overcoming chemoresistance and modulating the immuno-microenvironment. This strategy targets the heterogeneous distribution of CSCs and MDSCs in solid tumors, enhancing chemo-intervention and immune checkpoint blockade therapy while presenting encouraging potential for cascade deep tumor penetration and differentiation therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.