It has been said that polymers cannot be intelligent. They are, after all, just long chains of monomers with a few modifications. It is the researcher who is intelligent, utilizing the polymers for specific applications they are best suited for.

This website is dedicated to polymers brought to you by PolySciTech which seem to display intelligent properties such as targeted delivery or unique interactions in the right conditions.

Article 1
by Amie Tyler (PolySciTech)

Folate Receptors in Cancer Cells

Folate is a nutrient required by all living cells, and it is essential for cellular division. As represented in the image below, folate enters human cells via two distinct transport systems, the reduced folate carrier pathway, or RFC, which has low affinity for folate and the folate receptor pathway, which has high-affinity for folate.

The RFC is the principal route by which normal cells access folate circulating in the body. The RFC is a transport protein that is present on virtually all cells in the body.

In contrast, rapidly dividing cancer cells over-express the high-affinity folate receptor. The folate receptor captures folate from outside the cell and transports it inside by engulfing it within a vesicle called an endosome. Once internalized, the folate receptor releases the folate and is then recycled back to the cell surface where it resumes its function of capturing circulating folate.

Cellular Update of Folate
Figure 1. Endocytosis of folate carrier into the cell [1]
(SMDC: Small Molecule Drug Conjugates)
Base illustration courtesy Endocyte.

The vitamin folic acid (folate) has been widely researched as a targeting moiety for various anti-cancer drugs. Passively targeted NPs (nanoparticles) that have accumulated in the solid tumor might be more readily taken up by tumor cells by folate receptor-mediated endocytosis [2]. The receptor-mediated endocytic transfer is a widely utilized approach and the folate receptor on the cell membrane is a potential molecular target for tumor-selective drug delivery [3]. The folate conjugated NPs with the size less than 100 nm could be effective for achieving tumor specific delivery. This suggests that the difference in tumor concentrations between the targeted and the non-targeted polymer conjugates is due to the specific uptake of these molecules through the folate receptor abundant in the tumor. Distribution in all other tissues was not significantly changed by the delivery of free folic acid before the injection of the targeted conjugate. So the target drug increases its antitumor activity and significantly decreases its toxicity in normal tissues, allowing therapeutic responses not possible with a free drug [4].

The folate conjugates have proven to be highly potent and nontoxic to normal tissues. Two folate targeted drugs are currently in human clinical trials for various types of cancer [5]

Folate structure

Folate chemical structure diagram

Targeting

Products developed at the PolySciTech Division of Akina, Inc., for the purposes of studying drug release systems are primarily focused on creating intermediates for easy application of Folate-PEG-(***) targeting to your drug delivery system.

References

[1] ENDOCYTE INC - 10-K - 20110318 - BUSINESS

[2] Yoo, H.S.; Park, T.G. Folate-receptor-targeted delivery of doxorubicin nanoaggregates stabilized by doxorubicin–PEG–folate conjugate. J. Control. Release, 2004,100, 247.

[3] Yokoyama, M.; Okano, T.; Sakurai, Y.; Fukushima, S.; Okamoto, K.; Kataoka, K. Selective delivery of adiramycin to a solid tumor using a polymeric micelle carrier system. J. Drug Target, 1999, 7, 171.

[4] Kukowska-Latallo, J.F.; Candido, K. A.; Cao, Z.; Nigavekar, S. S.; Majoros, I. J.; Thomas, T. P.; Balogh, L. P.; Khan, M. K.; Baker Jr., J.R. Nanoparticle Targeting of Anticancer Drug Improves Therapeutic Response in Animal Model of Human Epithelial Cancer (Cancer Res 2005; 65(12): 5317-24)

[5] Dr. Philip S. Low, Ralph C. Corley Distinguished Professor of Biochemistry, Purdue University

Useful Full-Text Links

Doxorubicin-Loaded Polymeric Micelle Overcomes Multidrug Resistance of Cancer by Double-Targeting Folate Receptor and Early Endosomal pH
Dongin Kim, Eun Seong Lee, Kyung Taek Oh, Zhong Gao Gao, and You Han Bae

Folate-targeted chemotherapy Christopher P. Leamon, Joseph A. Reddy

Tumor cell targeting of liposome-entrapped drugs with phospholipid-anchored folic acid–PEG conjugates
Alberto Gabizon, Hilary Shmeeda, Aviva T. Horowitz, Samuel Zalipsky

Folate Receptor Targeted Imaging Using Poly (ethylene glycol)-folate: In Vitro and In Vivo Studies
Se-Lim Kim, Hwan-Jeong Jeong, Eun-Mi Kim, Chang-Moon Lee, Tae-Hyoung Kwon, and Myung-Hee Sohn

Controlled targeting of liposomal doxorubicin via the folate receptor in vitro
Justin M. Saul, Ananth Annapragada, Jayaganesh V. Natarajan, Ravi V. Bellamkondaa

More articles on this subject can be found in this Google Scholar query.


Art Project 1

The Music of Methoxy Poly(ethylene glycol)-b-Polycaprolactone

AK01


mPEG-PCL (PolyVivo AK01)