title: Effects of nanoparticle size on antitumor activity of 10-hydroxycamptothecin-conjugated gold nanoparticles: in vitro and in vivo studies.
abstract: Gold nanoparticles (AuNPs) have emerged as a promising anticancer drug delivery scaffold. However, some controversial points still require further investigation before clinical use. A complete understanding of how animal cells interact with drug-conjugated AuNPs of well-defined sizes remains poorly understood. In this study, we prepared a series of 10-hydroxycamptothecin (HCPT)-AuNP conjugates of different sizes and compared their cytotoxic effect in vitro and antitumor effect in vivo. Transmission electron micrographs showed that the NPs had a round, regular shape with a mean diameter of ~10, 25, and 50 nm. An in vitro drug release study showed that HCPT was continuously released for 120 hours. HCPT-AuNPs showed greater cytotoxic effects on the MDA-MB-231 cell line compared with an equal dose of free HCPT. Notably, HCPT-AuNPs of an average diameter of 50 nm (HCPT-AuNPs-50) had the greatest effect. Furthermore, administration of HCPT-AuNPs-50 showed the most tumor-suppressing activity against MDA-MB-231 tumor in mice among all treatment groups. The results indicate that AuNPs not only act as a carrier but also play an active role in mediating biological effects. This work gives important insights into the design of nanoscale delivery and therapeutic systems.
authors.affiliation: Department of Clinical Pharmacology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China; Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China.
authors.forename: Hanmei
authors.initials: H
authors.lastname: Bao
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China; Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China; Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Clinical Pharmacology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China; Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yan
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006046:Gold / Q000737:chemistry*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D010316:Particle Size
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D006046:Gold; C028098:10-hydroxycamptothecin; D002166:Camptothecin
keywords: cancer treatment; drug delivery; drug-containing nanocomposites; particle size