Academic Journal
Transcytosable Peptide-Paclitaxel Prodrug Nanoparticle for Targeted Treatment of Triple-Negative Breast Cancer.
| Title: | Transcytosable Peptide-Paclitaxel Prodrug Nanoparticle for Targeted Treatment of Triple-Negative Breast Cancer. |
|---|---|
| Authors: | Wang L; Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China., Zhao C; Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China., Lu L; Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China., Jiang H; Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China., Wang F; Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China., Zhang X; Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmacology, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China. |
| Source: | International journal of molecular sciences [Int J Mol Sci] 2023 Feb 28; Vol. 24 (5). Date of Electronic Publication: 2023 Feb 28. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI, [2000- |
| MeSH Terms: | Paclitaxel*/administration & dosage , Prodrugs*/administration & dosage , Triple Negative Breast Neoplasms*/drug therapy , Nanoparticle Drug Delivery System*/administration & dosage , Oligopeptides*/administration & dosage, Humans ; Cell Line, Tumor ; Nanoparticles/administration & dosage |
| Abstract: | Triple-negative breast cancer (TNBC) is an extremely aggressive subtype associated with a poor prognosis. At present, the treatment for TNBC mainly relies on surgery and traditional chemotherapy. As a key component in the standard treatment of TNBC, paclitaxel (PTX) effectively inhibits the growth and proliferation of tumor cells. However, the application of PTX in clinical treatment is limited due to its inherent hydrophobicity, weak penetrability, nonspecific accumulation, and side effects. To counter these problems, we constructed a novel PTX conjugate based on the peptide-drug conjugates (PDCs) strategy. In this PTX conjugate, a novel fused peptide TAR consisting of a tumor-targeting peptide, A7R, and a cell-penetrating peptide, TAT, is used to modify PTX. After modification, this conjugate is named PTX-SM-TAR, which is expected to improve the specificity and penetrability of PTX at the tumor site. Depending on hydrophilic TAR peptide and hydrophobic PTX, PTX-SM-TAR can self-assemble into nanoparticles and improve the water solubility of PTX. In terms of linkage, the acid- and esterase-sensitive ester bond was used as the linking bond, with which PTX-SM-TAR NPs could remain stable in the physiological environment, whereas PTX-SM-TAR NPs could be broken and PTX be released at the tumor site. A cell uptake assay showed that PTX-SM-TAR NPs were receptor-targeting and could mediate endocytosis by binding to NRP-1. The vascular barrier, transcellular migration, and tumor spheroids experiments showed that PTX-SM-TAR NPs exhibit great transvascular transport and tumor penetration ability. In vivo experiments, PTX-SM-TAR NPs showed higher antitumor effects than PTX. As a result, PTX-SM-TAR NPs may overcome the shortcomings of PTX and present a new transcytosable and targeted delivery system for PTX in TNBC treatment. |
| References: | Pharmacol Ther. 2019 Jul;199:30-57. (PMID: 30825473) Int J Pharm. 2017 Jun 30;526(1-2):474-495. (PMID: 28501439) J Am Chem Soc. 2021 Jan 20;143(2):538-559. (PMID: 33370092) Front Oncol. 2021 Apr 12;11:654672. (PMID: 33912463) J Control Release. 2022 Feb;342:280-294. (PMID: 35016919) Nanomedicine. 2020 Feb;24:102120. (PMID: 31676374) Med Oncol. 2022 Dec 2;40(1):25. (PMID: 36456774) Expert Opin Investig Drugs. 2020 Nov;29(11):1199-1208. (PMID: 32869671) Nat Nanotechnol. 2019 Aug;14(8):799-809. (PMID: 31263194) Sci China Life Sci. 2021 Mar;64(3):372-388. (PMID: 32803712) Curr Med Chem. 2017;24(31):3373-3396. (PMID: 28393694) Int J Nanomedicine. 2020 Nov 12;15:8875-8892. (PMID: 33209022) Nano Lett. 2019 Nov 13;19(11):8010-8020. (PMID: 31639306) Sci Transl Med. 2021 Sep 08;13(610):eabd4811. (PMID: 34516829) Asian J Pharm Sci. 2019 Nov;14(6):595-608. (PMID: 32104486) Methods Mol Biol. 2021;2207:327-338. (PMID: 33113145) Acta Pharm Sin B. 2020 Aug;10(8):1563-1575. (PMID: 32963950) Int J Mol Sci. 2017 Aug 09;18(8):. (PMID: 28792473) Expert Opin Drug Deliv. 2022 Feb;19(2):147-161. (PMID: 35130795) Toxicol Appl Pharmacol. 2023 Feb 1;460:116376. (PMID: 36638973) J Pharm Sci. 2015 Mar;104(3):1160-73. (PMID: 25449709) Eur J Med Chem. 2021 Mar 5;213:113050. (PMID: 33280896) Adv Drug Deliv Rev. 2017 Feb;110-111:112-126. (PMID: 27370248) Exp Hematol Oncol. 2022 Nov 8;11(1):93. (PMID: 36348391) Biomacromolecules. 2020 Dec 14;21(12):5119-5127. (PMID: 33174734) Life Sci. 2021 Apr 1;270:119113. (PMID: 33508290) Ther Adv Med Oncol. 2020 May 11;12:1758835920915980. (PMID: 32426047) Cancer Lett. 2021 Jan 28;497:100-111. (PMID: 33069769) Sci Rep. 2017 Jun 12;7(1):3301. (PMID: 28607365) Breast Cancer Res. 2020 Jun 9;22(1):61. (PMID: 32517735) Semin Cancer Biol. 2021 Jul;72:136-145. (PMID: 32544511) Target Oncol. 2016 Aug;11(4):501-5. (PMID: 26916409) Chem Soc Rev. 2021 Feb 15;50(3):1480-1494. (PMID: 33346298) Int J Pharm. 2021 Jan 25;593:120141. (PMID: 33279713) Molecules. 2020 Dec 17;25(24):. (PMID: 33348838) Curr Treat Options Oncol. 2019 Nov 21;20(11):82. (PMID: 31754897) J Drug Target. 2021 Feb;29(2):155-167. (PMID: 32838575) Drug Deliv. 2017 Nov;24(1):752-764. (PMID: 28468542) Front Chem. 2020 Jul 07;8:571. (PMID: 32733853) Int J Mol Sci. 2023 Jan 03;24(1):. (PMID: 36614268) J Med Chem. 2021 Jan 14;64(1):216-232. (PMID: 33382619) Polymers (Basel). 2022 Feb 09;14(4):. (PMID: 35215570) J Biol Chem. 2003 Dec 5;278(49):48848-60. (PMID: 14514674) J Control Release. 2017 Mar 28;250:62-76. (PMID: 28167286) Adv Sci (Weinh). 2020 Dec 21;8(3):2001960. (PMID: 33552853) Front Med. 2021 Feb;15(1):1-10. (PMID: 32789731) Arch Pharm Res. 2023 Jan;46(1):18-34. (PMID: 36593377) Molecules. 2022 Oct 25;27(21):. (PMID: 36364057) Cancers (Basel). 2020 Aug 24;12(9):. (PMID: 32846967) Theranostics. 2019 Oct 17;9(26):8073-8090. (PMID: 31754382) Clin Breast Cancer. 2021 Oct;21(5):383-390. (PMID: 33781662) |
| Grant Information: | 82273835 National Natural Science Foundation of China; ZR2020MH404 National Natural Science Foundation of Shandong Province |
| Contributed Indexing: | Keywords: A7R peptide; TAT peptide; anticancer therapy; paclitaxel; peptide-drug conjugate; targeted delivery; transcytosis |
| Substance Nomenclature: | P88XT4IS4D (Paclitaxel) 0 (Prodrugs) 0 (Nanoparticle Drug Delivery System) 0 (Ala-Thr-Trp-Leu-Pro-Pro-Arg) 0 (Oligopeptides) |
| Entry Date(s): | Date Created: 20230311 Date Completed: 20230410 Latest Revision: 20230410 |
| Update Code: | 20230411 |
| PubMed Central ID: | PMC10003159 |
| DOI: | 10.3390/ijms24054646 |
| PMID: | 36902076 |
| Database: | MEDLINE |
| Full text is not displayed to guests. | Login for full access. |
Accede al texto completo | ISSN: | 1422-0067 |
|---|---|
| DOI: | 10.3390/ijms24054646 |