Surface-Functionalized Carrier-Free Drug Nanorods for Leukemia

被引：10

作者：

Krishnan, Vinu ^{[1
,2
,3
]}

Sarode, Apoorva ^{[1
,2
,3
]}

Bhatt, Rohit ^{[2
]}

Oliveira, Joshua D. ^{[1
,2
]}

Brown, Tyler D. ^{[2
,3
,4
]}

Jiang, Y. P. ^{[5
]}

Junutula, Jagath Reddy ^{[5
]}

Mitragotri, Samir ^{[1
,2
,3
]}

机构：

[1] Univ Calif Santa Barbara, Dept Chem Engn, Engn 2 Bldg, Santa Barbara, CA 93106 USA

[2] Univ Calif Santa Barbara, Ctr Bioengn, Santa Barbara, CA 93106 USA

[3] Harvard Univ, John A Paulson Sch Engn & Appl Sci, Cambridge, MA 02138 USA

[4] Univ Calif Santa Barbara, Biomol Sci & Engn, Santa Barbara, CA 93106 USA

[5] Cellerant Therapeut Inc, 1561 Ind Rd, San Carlos, CA 94070 USA

来源：

ADVANCED THERAPEUTICS | 2018年 / 1卷 / 02期

关键词：

acute myeloid leukemia; AML; camptothecin; carrier-free drug delivery; CD33; Hu195; nanorods; PEGylation; HUMAN SERUM; PHASE-I; THERAPEUTIC-EFFICACY; BINDING-PROPERTIES; ANTITUMOR-ACTIVITY; MYELOID-LEUKEMIA; CHIMERIC PEPTIDE; ANTIBODY HUM195; CAMPTOTHECIN; TRIAL;

D O I：

10.1002/adtp.201800010

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Pure drug nanoparticles have emerged as an alternate method for formulating extremely hydrophobic drugs. Herein, a simple and efficient process for synthesizing PEGylated and antibody-conjugated, carrier-free nanomedicine is reported as a promising strategy to deliver the drug, Camptothecin (CPT) for aggressive circulating tumors such as Acute Myeloid Leukemia (AML). Size, shape, and surface morphology of pure drug nanorods (NRs) are examined and characterized by a variety of techniques. Incorporation of polyethylene glycol (PEG) onto the particle changed its surface charge and topography while affecting its drug-dissolution kinetics. Furthermore, the toxicity of PEGylated versus non-PEGylated forms of humanized anti-CD33 antibody (Hu195Ab)-coated CPT NRs are compared. Hu195Ab drug-linked NRs increased cell killing in leukemic cells and surface PEGylation show reduced non-specific uptake in cells. The results demonstrate that surface-modified carrier-free nanodrugs could have significant implications in cancer drug delivery for treating AML. This would be the first instance of studying the potential of surface-functionalized carrier-free drug NRs in the treatment of leukemia.

引用

页数：10