An albumin nanocomplex-based endosomal pH-activatable on/off probe system.
Albumin has gained considerable interest as a material for fabricating nanoparticulate systems due to its biomedical advantages, such as biocompatibility and chemical functionality. Here, we report a new pH-sensitive albumin nanocomplex prototype with a zinc-imidazole coordination bond. Albumin was conjugated with 1-(3-aminopropyl)imidazole and mPEG10kDa-NHS, and the resulting albumin conjugate (PBI) was then modified with either Cy5.5 or BHQ-3. The newly formed albumin nanocomplex (C/BQ-PBI Zn NCs: ∼116nm) system was facilely self-assembled around pH 7.4 in the presence of Zn(2+), but it quickly disassembled in an acidic environment (∼pH 5.0). Based on this pH-sensitivity, C/BQ-PBI Zn NCs emitted strong near-infrared fluorescence and released Zn(2+), turning "off" at pH ∼7.4 (e.g., plasma) and "on" at pH ∼5.0 (e.g., endo/lysosomes in tumor cells) on account of fluorescence resonance energy transfer. C/BQ-PBI Zn NCs displayed significant cytotoxicity due to an increase in cellular Zn(2+) in response to endosomal pH (∼5.0) in breast cancer MCF-7 cells and lung adenocarcinoma A549 cells. Particularly, confocal laser scanning microscopic images showed a strong fluorescence signal caused by the disassembly of C/BQ-PBI Zn NCs in the endosomal region of MCF-7 cells. Based on these results, we believe that this albumin nanocomplex is an attractive biocompatible tumor targeting probe carrier for the theranostic purpose.
School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 16419, Republic of Korea.
Changkyu
C
Lee
School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 16419, Republic of Korea.
Seunghyun
S
Lee
School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 16419, Republic of Korea.
Le Quang
LQ
Thao
School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 16419, Republic of Korea.
Ha Shin
HS
Hwang
College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 38541, Republic of Korea.
Jong Oh
JO
Kim
Division of Biotechnology, The Catholic University of Korea, 43-1 Yeokgok 2-dong, Wonmi-gu, Bucheon-si, Gyeonggi-do 14662, Republic of Korea.
Eun Seong
ES
Lee
College of Pharmacy, Chung-Ang University, 221 Heukseok dong, Dongjak-gu, Seoul 06974, Republic of Korea.
Kyung Taek
KT
Oh
College of Pharmacy, Catholic University of Daegu, 330 Geumrak 1-ri, Hayang Eup, Gyeongsan si, Gyeongbuk 38430, Republic of Korea.
Beom Soo
BS
Shin
College of Pharmacy, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan 15588, Republic of Korea.
Han-Gon
HG
Choi
School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 16419, Republic of Korea. Electronic address: ysyoun@skku.edu.
Yu Seok
YS
Youn
D000072283:A549 Cells; D000818:Animals; D002417:Cattle; D016923:Cell Death; D011992:Endosomes / Q000378:metabolism*; D005453:Fluorescence; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000737:chemistry; D061986:MCF-7 Cells; D015335:Molecular Probes / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D020005:Propanols / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry
C515394:1-(3-aminopropyl)imidazole; D007093:Imidazoles; D015335:Molecular Probes; D020005:Propanols; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; D015032:Zinc
Albumin; Nanocomplex; Self-assembly; Tumor targeting; Zinc-imidazole interaction; pH-sensitivity