Tumor-targeting peptide conjugated pH-responsive micelles as a potential drug carrier for cancer therapy

Xiang Lan Wu, Jong Ho Kim, Heebeom Koo, Sang Mun Bae, Hyeri Shin, Min Sang Kim, Byung Heon Lee, Rang Woon Park, In-San Kim, Kuiwon Choi, Ick Chan Kwon, Kwang Meyung Kim, Doo Sung Lee

Research output: Contribution to journalArticle

176 Citations (Scopus)

Abstract

Herein, we prepared tumor-targeting peptide (AP peptide; CRKRLDRN) conjugated pH-responsive polymeric micelles (pH-PMs) in cancer therapy by active and pH-responsive tumor targeting delivery systems, simultaneously. The active tumor targeting and tumoral pH-responsive polymeric micelles were prepared by mixing AP peptide conjugated PEG-poly(D,L-lactic acid) block copolymer (AP-PEG-PLA) into the pH-responsive micelles of methyl ether poly(ethylene glycol) (MPEG)-poly(βamino ester) (PAE) block copolymer (MPEG-PAE). These mixed amphiphilic block copolymers were self-assembled to form stable AP peptide-conjugated and pH-responsive APPEG- PLA/MPEG-PAE micelles (AP-pH-PMs) with an average size of 150 nm. The AP-pH-PMs containing 10 wt % of AP-PEG-PLA showed a sharp pH-dependent micellization/demicellization transition at the tumoral acid pH. Also, they presented the pH-dependent drug release profile at the acidic pH of 6.4. The fluorescence dye, TRITC, encapsulated AP-pH-PMs (TRITC-AP-pH-PMs) presented the higher tumor-specific targeting ability in vitro cancer cell culture system and in vivo tumor-bearing mice, compared to control pH-responsive micelles of MPEG-PAE. For the cancer therapy, the anticancer drug, doxorubicin (DOX), was efficiently encapsulated into the AP-pH-PMs (DOX-AP-pH-PMs) with a higher loading efficiency. DOX-AP-pH-PMs efficiently deliver anticancer drugs in MDA-MB231 human breast tumor-bearing mice, resulted in excellent anticancer therapeutic efficacy, compared to free DOX and DOX encapsulated MEG-PAE micelles, indicating the excellent tumor targeting ability of AP-pH-PMs. Therefore, these tumor-targeting peptide-conjugated and pH-responsive polymeric micelles have great potential application in cancer therapy.

Original languageEnglish
Pages (from-to)208-213
Number of pages6
JournalBioconjugate Chemistry
Volume21
Issue number2
DOIs
Publication statusPublished - 2010 Feb 17
Externally publishedYes

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Drug Carriers
Micelles
Peptides
Tumors
Neoplasms
Doxorubicin
Esters
Polyethylene glycols
Therapeutics
Bearings (structural)
Block copolymers
Pharmaceutical Preparations
Methyl Ethers
Micellization
Lactic acid
methoxy poly(ethylene glycol)-poly(lactide)
monomethoxypolyethylene glycol
Cell culture
Ethers
Ethylene Glycol

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Organic Chemistry
  • Pharmaceutical Science
  • Biomedical Engineering
  • Pharmacology

Cite this

Wu, X. L., Kim, J. H., Koo, H., Bae, S. M., Shin, H., Kim, M. S., ... Lee, D. S. (2010). Tumor-targeting peptide conjugated pH-responsive micelles as a potential drug carrier for cancer therapy. Bioconjugate Chemistry, 21(2), 208-213. https://doi.org/10.1021/bc9005283

Tumor-targeting peptide conjugated pH-responsive micelles as a potential drug carrier for cancer therapy. / Wu, Xiang Lan; Kim, Jong Ho; Koo, Heebeom; Bae, Sang Mun; Shin, Hyeri; Kim, Min Sang; Lee, Byung Heon; Park, Rang Woon; Kim, In-San; Choi, Kuiwon; Kwon, Ick Chan; Kim, Kwang Meyung; Lee, Doo Sung.

In: Bioconjugate Chemistry, Vol. 21, No. 2, 17.02.2010, p. 208-213.

Research output: Contribution to journalArticle

Wu, XL, Kim, JH, Koo, H, Bae, SM, Shin, H, Kim, MS, Lee, BH, Park, RW, Kim, I-S, Choi, K, Kwon, IC, Kim, KM & Lee, DS 2010, 'Tumor-targeting peptide conjugated pH-responsive micelles as a potential drug carrier for cancer therapy', Bioconjugate Chemistry, vol. 21, no. 2, pp. 208-213. https://doi.org/10.1021/bc9005283
Wu, Xiang Lan ; Kim, Jong Ho ; Koo, Heebeom ; Bae, Sang Mun ; Shin, Hyeri ; Kim, Min Sang ; Lee, Byung Heon ; Park, Rang Woon ; Kim, In-San ; Choi, Kuiwon ; Kwon, Ick Chan ; Kim, Kwang Meyung ; Lee, Doo Sung. / Tumor-targeting peptide conjugated pH-responsive micelles as a potential drug carrier for cancer therapy. In: Bioconjugate Chemistry. 2010 ; Vol. 21, No. 2. pp. 208-213.
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