Combination chemotherapy with cisplatin and chloroquine: Effect of encapsulation in micelles formed by self-assembling hybrid dendritic–linear–dendritic block copolymers

González-Pastor R. ; Lancelot A. ; Morcuende-Ventura V. ; San Anselmo M (Universidad de Zaragoza) ; Sierra T. ; Serrano J.L. (Universidad de Zaragoza) ; Martin-Duque P.

Resumen: Clinical outcomes of conventional drug combinations are not ideal due to high toxicity to healthy tissues. Cisplatin (CDDP) is the standard component for many cancer treatments, yet its principal dose-limiting side effect is nephrotoxicity. Thus, CDDP is commonly used in combination with other drugs, such as the autophagy inhibitor chloroquine (CQ), to enhance tumor cell killing efficacy and prevent the development of chemoresistance. In addition, nanocarrier-based drug delivery systems can overcome chemotherapy limitations, decreasing side effects and increasing tumor accumulation. The aim of this study was to evaluate the toxicity of CQ and CDDP against tumor and non-tumor cells when used in a combined treatment. For this purpose, two types of mi-celles based on Pluronic® F127 hybrid dendritic–linear–dendritic block copolymers (HDLDBCs) modified with polyester or poly(esteramide) dendrons derived from 2, 2'-bis(hydroxymethyl)propi-onic acid (HDLDBC-bMPA) or 2, 2'-bis(glycyloxymethyl)propionic acid (HDLDBC-bGMPA) were explored as delivery nanocarriers. Our results indicated that the combined treatment with HDLDBC-bMPA(CQ) or HDLDBC-bGMPA(CQ) and CDDP increased cytotoxicity in tumor cells compared to the single treatment with CDDP. Encapsulations demonstrated less short-term cyto-toxicity individually or when used in combination compared to the free drugs. However, and more importantly, a low degree of cytotoxicity against non-tumor cells was maintained, even when drugs were given simultaneously.

Idioma: Inglés

DOI: 10.3390/ijms22105223

Año: 2021

Publicado en: International Journal of Molecular Sciences 22, 10 (2021), 5223 [19 pp.]
ISSN: 1661-6596

Factor impacto JCR: 6.208 (2021)

Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 69 / 297 = 0.232 (2021) - Q1 - T1
Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 50 / 179 = 0.279 (2021) - Q2 - T1

Factor impacto CITESCORE: 6.9 - Computer Science (Q1) - Chemical Engineering (Q1) - Medicine (Q1) - Biochemistry, Genetics and Molecular Biology (Q2)

Factor impacto SCIMAGO: 1.176 - Computer Science Applications (Q1) - Inorganic Chemistry (Q1) - Spectroscopy (Q1) - Organic Chemistry (Q1) - Physical and Theoretical Chemistry (Q1) - Molecular Biology (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA/E47-20R
Financiación: info:eu-repo/grantAgreement/ES/UZ-DGA/T57-17R-P
Financiación: info:eu-repo/grantAgreement/ES/ISCIII-FEDER-PI19-01007
Financiación: info:eu-repo/grantAgreement/ES/MICINN-FEDER/PGC2018-093761-B-C31
Financiación: info:eu-repo/grantAgreement/ES/MICINN-FEDER/PGC2018-097583-B-I00

Tipo y forma: Article (Published version)

Área (Departamento): Área Química Orgánica (Dpto. Química Orgánica)