Polymer–drug conjugates: Origins, progress to date and future directions

Kopeček, Jindřich

doi:10.1016/j.addr.2012.10.014

Cited by 328 publications

(230 citation statements)

References 180 publications

(182 reference statements)

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“…However, there was nonspecific uptake in the liver and lymph nodes of the near infrared (NIR) dyes, which could limit their use in specific tumor imaging. Since polyethylene glycol (PEG) conjugation can alter the pharmacokinetics and biodistribution of molecules, [2][3][4][5][6][7] we hypothesized that the polyethylene glycol linkage (PEGylation) of NIR dyes conjugated with anti-CEA antibodies could enable enhanced tumor labeling in a nude mouse model of human pancreatic cancer, which is the subject of the present report.…”

Section: Introductionmentioning

confidence: 99%

Specific tumor labeling enhanced by polyethylene glycol linkage of near infrared dyes conjugated to a chimeric anti-carcinoembryonic antigen antibody in a nude mouse model of human pancreatic cancer

et al. 2014

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Abstract. Labeling of metastatic tumors can aid in their staging and resection of cancer. Near infrared (NIR) dyes have been used in the clinic for tumor labeling. However, there can be a nonspecific uptake of dye by the liver, lungs, and lymph nodes, which hinders detection of metastasis. In order to overcome these problems, we have used two NIR dyes (DyLight 650 and 750) conjugated to a chimeric anti-carcinoembryonic antigen antibody to evaluate how polyethylene glycol linkage (PEGylation) can improve specific tumor labeling in a nude mouse model of human pancreatic cancer. The conjugated PEGylated and non-PEGylated DyLight 650 and 750 dyes were injected intravenously into non-tumor-bearing nude mice. Serum samples were collected at various time points in order to determine serum concentrations and elimination kinetics. Conjugated PEGylated dyes had significantly higher serum dye concentrations than non-PEGylated dyes (p ¼ 0.005 for the 650 dyes and p < 0.001 for the 750 dyes). Human pancreatic tumors subcutaneously implanted into nude mice were labeled with antibody-dye conjugates and serially imaged. Labeling with conjugated PEGylated dyes resulted in significantly brighter tumors compared to the non-PEGylated dyes (p < 0.001 for the 650 dyes; p ¼ 0.01 for 750 dyes). PEGylation of the NIR dyes also decreased their accumulation in lymph nodes, liver, and lung. These results demonstrate enhanced selective tumor labeling by PEGylation of dyes conjugated to a tumor-specific antibody, suggesting their future clinical use in fluorescence-guided surgery.

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Section: Introductionmentioning

confidence: 99%

Specific tumor labeling enhanced by polyethylene glycol linkage of near infrared dyes conjugated to a chimeric anti-carcinoembryonic antigen antibody in a nude mouse model of human pancreatic cancer

et al. 2014

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“…More recently, HPMA polymers have been proposed as drug-free macromolecular therapeutics for the treatment of B cell non-Hodgkin lymphoma (NHL) (84,85). This approach is based on the principal that crosslinking of CD20 antigens, a biomarker expressed by most malignant B cells, causes cell apoptosis (86).…”

Section: N-(2-hydroxypropyl) Mathacrylamide Copolymer Assemliesmentioning

confidence: 99%

Drug Carriers: Not an Innocent Delivery Man

Yeo

Kim

2015

AAPS J

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Abstract. Biomaterials used as drug carriers are often considered inactive and assumed to have no other roles than modifying pharmacokinetics and biodistribution of a drug. On the other hand, there are several examples in which the carrier materials show bioactivities in the body, which may have been underestimated or inadvertently ignored. This review highlights several examples where biomaterials used as drug carriers bring biological effects, known or newly discovered, and discusses their implications in development of new drug delivery systems.

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“…Consequently, the interaction and recognition effects of the P-glycoprotein efflux pump toward such macromolecules are minimized. [28][29][30] Furthermore, the pH responsivity of conjugates tends to trigger effective drug release in acid tumor cells and concentrates the intracellular drug to a sufficiently high level, 31,32 see Figure 2. The final conjugate was synthesized in four steps (Figure 3).…”

Section: Introductionmentioning

confidence: 99%