[생명공학] Cancer cell Imaging & Treatment(영문)
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추천 연관자료
- 목차
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1. Introduction
2. Cancer Cell Targeting
2.1. Basic ideas of cancer treatment research
2.2. Drug targeting
3. Problem and things to be advanced
4. Mechanism
4.1. Linking the Domains
4.2. Functions of Domains
4.3. Stepwise Mechanism of Molecular Complex
5. Conclusion
6. Reference
- 본문내용
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(2) Active targeting
Nanoparticle passive targeting can be enhanced by ‘active targeting’, where specific ligands (peptides, antibodies, aptamers, or small molecules) are attached to the nanoparticle surface to bind receptors/antigens overexpressed on cancer cells. Targeting increases accumulation in tumors and lessens exposure to healthy tissue, which can improve a toxic drug’'s therapeutic index and reduce adverse side effects.
According to its importance, many researches these days are trying to identify and develop specific antigens and receptors that are unique to cancer cells. The decoration of nanoparticles with tumor targeting molecules, such as hormones, growth factors etc. can increase the efficacy of a treatment. Integrin, EGFR are usually the target receptors.
Figure 3 A description of passive and active targeting. Blood vessel near tumor is not well organized, and numbers of pores are found. EPR effect is observed only at the tumor tissue. Through this effect, drugs are accumulated.
3. Problem and things to be advanced
We cover the meaning of cancer targeting, and how to target cancer. Nowadays, there are many not only drugs but also treatments for cancer treatment, but they have some problems.
1. Chemical-based Anticancer drugs
These chemical-based drugs are systemic drug. Therefore, normal cells are also regarded as cancer cells and become treated. Normal cells are attacked by chemical-drug, and then many cells are damaged. It brings out many side effects. The patient gets a lot pain when he or she receives anticancer treatments
2. Drugs Detecting Receptors on Cancer Cell’s Surface
The receptors, which is important to cancer targeting, exist not only on the cancer cell’s surface but also on the normal cell’s surface. So we have a potential to mis-treatment.
So, we focused on overcoming of these drawbacks. To overcome these side effects we considered two things.
1. Nano-sized particle
Nano-sized particle is the method for passive targeting. So our final molecule should be less than 200~300nm in order to pass the pores of abnormal vessels. These nano-sized particles can detect cancer cell because of EPR effect. So size of particles is important.
2. Integrin αvβ3
Integrin αvβ3 is the method for active targeting. Most of cancer cell have these receptor. Selection of molecules which target this receptor should be made.
For our strategy to use double targeting, we use special peptide pHLIP(pH Low Insertion Peptide). Cancer cells accumulate pyruvate due to insufficient O2 and consequent decrease of oxidative phosphorylation. So H+ pumps transport protons to extracellular fluid to maintain normal cytoplasmic pH.
Thus, Tumor acidity is a specific tumor biomarker. pHLIP is pH-dependent molecule, so it detects the concentration change of proton. If pH is lower in extracellular surface, this molecule enters into phospholipid bilayer due to transmembrane part containing uncharged Asp by
- 참고문헌
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[1] Kumar, V., Cotran, R.S., and Robbins, S.L. (2003), Robbins Basic Pathology, PA : Saunders.
[2] Fauci, A.S. (2008), Harrison’s Principles of Internal Medicine, NY : McGraw-Hill Medical.
[3] Katzung, B.G. (2007), Basic & Clinical Pharmacology, NY : McGraw-Hill
[4] Hillery, A. M., Lloyd, A. W., and Swarbrick, J. (2001), Drug delivery and targeting for pharmacists and pharmaceutical scientists, New York : Taylor&Francis.
[5] Adiseshaiah, P. P., Hall, J. B., and McNeil, S. E. (2009), Nanomaterial standards for efficacy and toxicity assessment.
[6] Kwon G. S. (2005), Polymeric drug delivery systems, New York : Taylor&Francis.
[7] Gregoriadis, G., McCormack, B. (1998), Targeting of drugs 6: strategies for stealth therapeutic systems, New York : Plenum Press.
[8]유미경, 박진호, 전상용, “암 진단용 자기공명영상 나노조영제”, 고분자과학과 기술, 19권 2호, 한국고분자학회, 2008.
[9] Enhanced permeability and retention effect, Wikipedia(www.wikipedia.org).
[10]http://www.kostat.go.kr/nso_main/nsoMainAction.do?method=search&catgrp=nso2009&catid1=k09___0000&catid2=k09i__0000&forward=search – 사망원인통계(전국편, 2008년) : 표5
[11] Reshetnyak, Y.K., Andreev, O.A., Lehnert, U., Engelman, D.M. Translocation of molecules into cells by pH-dependent insertion of a transmembrane helix. Proc. Natl. Acad. Sci. USA. 103, 6460-6465 (2006)
[12] Crasto, C.J., Feng, J. LINKER: a program to generate linker sequences for fusion proteins. Protein Engng. 13, 309-312 (2000).
[13] Sugahara, S., Kajiki, M., Kuriyama, H., Kobayashi, T. Paclitaxel Delivery Systems: The Use of Amino Acid Linkers in the Conjugation of Paclitaxel with Carboxymethyldextran to Create Prodrugs. Biol. Pharm. Bull. 25(5), 632-641 (2002).
[14]Hunt, J.F., et. al. Spontaneous, pH-dependent membrane insertion of a transbilayer α-helix. Biochemistry-US. 36, 15177-15192 (1997)
[15] Cheng, Kenneth T.. “Cy7-Tetrameric arginine-glycine-aspartic acid peptide [Cy7-E{E[c(RGDyK)]2}2]”. MICAD. 25 May 2010.
[16] Shan, Liang. “Cy5.5-labeled pH low insertion peptide (pHLIP)”. MICAD. 5 May 2010.
[17] Segala, J.. Accurate analysis of tumor margins using a fluorescent pH low insertion peptide(pHLIP). Int. J. Mol. Sci. 10, 3478-3487 (2009).
[18] Stolik S., et. al. Measurement of the penetration depths of red and near infrared light in human “ex vivo” tissues. J. Photoch. Photobio. B. 57, 90-93 (2000).
[19] Shakley, D.C.. Light penetration in bladder tissue: implications for the intravesical photodynamic therapy of bladder tumors. BJU Int. 86, 638-643 (2000).
[20] Shim, I.K. Ehwa Woman’s University, 25 May 2010. < dream.ewha.ac.kr/~epharm/cgi-bin/spboarda/board.cgi?id=pds&action=download&gul=1228>
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