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Makimoto A, Fang J, Maeda H. Development of a Selective Tumor-Targeted Drug Delivery System: Hydroxypropyl-Acrylamide Polymer-Conjugated Pirarubicin (P-THP) for Pediatric Solid Tumors. Cancers (Basel). 2021;13(15)doi: 10.3390/cancers13153698.
Makimoto, A., Fang, J., & Maeda, H. (2021). Development of a Selective Tumor-Targeted Drug Delivery System: Hydroxypropyl-Acrylamide Polymer-Conjugated Pirarubicin (P-THP) for Pediatric Solid Tumors. Cancers, 13(15), . https://doi.org/10.3390/cancers13153698
Makimoto, Atsushi, et al. "Development of a Selective Tumor-Targeted Drug Delivery System: Hydroxypropyl-Acrylamide Polymer-Conjugated Pirarubicin (P-THP) for Pediatric Solid Tumors." Cancers vol. 13,15 (2021). doi: https://doi.org/10.3390/cancers13153698
Makimoto A, Fang J, Maeda H. Development of a Selective Tumor-Targeted Drug Delivery System: Hydroxypropyl-Acrylamide Polymer-Conjugated Pirarubicin (P-THP) for Pediatric Solid Tumors. Cancers (Basel). 2021 Jul 23;13(15). doi: 10.3390/cancers13153698. PMID: 34359599; PMCID: PMC8345214.
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Cancers (Basel). 2021 Jul 23;13(15). doi: 10.3390/cancers13153698.

Development of a Selective Tumor-Targeted Drug Delivery System: Hydroxypropyl-Acrylamide Polymer-Conjugated Pirarubicin (P-THP) for Pediatric Solid Tumors.

Cancers

Atsushi Makimoto, Jun Fang, Hiroshi Maeda

Affiliations

  1. Department of Hematology/Oncology, Tokyo Metropolitan Children's Medical Center, Tokyo 183-8561, Japan.
  2. Faculty of Pharmaceutical Science, Sojo University, Kumamoto 860-0082, Japan.
  3. BioDynamics Research Foundation, Kumamoto 862-0954, Japan.
  4. Department of Microbiology, Kumamoto University School of Medicine, Kumamoto 862-0954, Japan.
  5. Tohoku University, Miyagi 980-8572, Japan.
  6. Faculty of Medicine, Osaka University, Osaka 565-0871, Japan.

PMID: 34359599 PMCID: PMC8345214 DOI: 10.3390/cancers13153698

Abstract

Most pediatric cancers are highly chemo-sensitive, and cytotoxic chemotherapy has always been the mainstay of treatment. Anthracyclines are highly effective against most types of childhood cancer, such as neuroblastoma, hepatoblastoma, nephroblastoma, rhabdomyosarcoma, Ewing sarcoma, and so forth. However, acute and chronic cardiotoxicity, one of the major disadvantages of anthracycline use, limits their utility and effectiveness. Hydroxypropyl acrylamide polymer-conjugated pirarubicin (P-THP), which targets tumor tissue highly selectively via the enhanced permeability and retention (EPR) effect, and secondarily releases active pirarubicin molecules quickly into the acidic environment surrounding the tumor. Although, the latter rarely occurs in the non-acidic environment surrounding normal tissue. This mechanism has the potential to minimize acute and chronic toxicities, including cardiotoxicity, as well as maximize the efficacy of chemotherapy through synergy with tumor-targeting accumulation of the active molecules and possible dose-escalation. Simply replacing doxorubicin with P-THP in a given regimen can improve outcomes in anthracycline-sensitive pediatric cancers with little risk of adverse effects, such as cardiotoxicity. As cancer is a dynamic disease showing intra-tumoral heterogeneity during its course, continued parallel development of cytotoxic agents and molecular targeting agents is necessary to find potentially more effective treatments.

Keywords: DDS; EPR effect; P-THP; anthracyclines; drug delivery system; enhanced permeability and retention effect; hydroxypropyl acrylamide polymer-conjugated pirarubicin; nanomedicine; pediatric cancers; targeted drug delivery

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