Combating HIV-1 Entry and Fusion with Peptide–Synthetic Polymer Conjugates

Author(s):  
Maarten Danial ◽  
Harm-Anton Klok
2012 ◽  
Vol 13 (5) ◽  
pp. 1438-1447 ◽  
Author(s):  
Maarten Danial ◽  
Michael J. Root ◽  
Harm-Anton Klok

2016 ◽  
Vol 89 (2) ◽  
pp. 1170-1177 ◽  
Author(s):  
Ahlam Alalwiat ◽  
Wen Tang ◽  
Selim Gerişlioğlu ◽  
Matthew L. Becker ◽  
Chrys Wesdemiotis

2006 ◽  
Vol 207 (18) ◽  
pp. 1629-1632 ◽  
Author(s):  
Akira Ono

2011 ◽  
Vol 12 (8) ◽  
pp. 2908-2913 ◽  
Author(s):  
Nikhil K. Singha ◽  
Matthew I. Gibson ◽  
Bishnu P. Koiry ◽  
Maarten Danial ◽  
Harm-Anton Klok

2007 ◽  
Vol 35 (1) ◽  
pp. 56-60 ◽  
Author(s):  
R. Duncan

Marriage of cell biology (the concept of ‘lysosomotropic drug delivery’) and the realization that water-soluble synthetic polymers might provide an ideal platform for targeted drug delivery led to the first synthetic polymer–drug conjugates that entered clinical trials as anticancer agents. Conceptually, polymer conjugates share many features with other macromolecular drugs, but they have the added advantage of the versatility of synthetic chemistry that allows tailoring of molecular mass and addition of biomimetic features. Conjugate characteristics must be optimized carefully to ensure that the polymeric carrier is biocompatible and that the polymer molecular mass enables tumour-selective targeting followed by endocytic internalization. The polymer–drug linker must be stable in transit, but be degraded at an optimal rate intracellularly to liberate active drug. Our early studies designed two HPMA [N-(2-hydroxypropyl)methacrylamide] copolymer conjugates containing doxorubicin that became the first synthetic polymer–drug conjugates to be tested in phase I/II clinical trials. Since, a further four HPMA copolymer–anticancer drug conjugates (most recently polymer platinates) and the first polymer-based γ-camera imaging agents followed. Polymer–drug linkers cleaved by lysosomal thiol-dependent proteases and the reduced pH of endosomes and lysosomes have been used widely to facilitate drug liberation. It is becoming clear that inappropriate trafficking and/or malfunction of enzymatic activation can lead to new mechanisms of clinical resistance. Recent studies have described HPMA copolymer conjugates carrying a combination of both endocrine and chemotherapy that are markedly more active than individual conjugates carrying a single drug. Moreover, current research is investigating novel dendritic polymer architectures and novel biodegradable polymers as drug carriers that will provide improved drug delivery and imaging probes in the future. The present paper reviews the clinical status of polymeric anticancer agents, the rationale for the design of polymer therapeutics and discusses the benefits and challenges of lysosomotropic delivery.


2000 ◽  
Vol 49 (5) ◽  
pp. 455-461,513
Author(s):  
Takeshi MORI ◽  
Mizuo MAEDA

1991 ◽  
Vol 24 (22) ◽  
pp. 6046-6049 ◽  
Author(s):  
Manssur Yalpani ◽  
Robert H. Marchessault ◽  
Frederick G. Morin ◽  
Clevys J. Monasterios

2007 ◽  
Vol 47 (1) ◽  
pp. 63-92 ◽  
Author(s):  
Jan C. M. van Hest

Author(s):  
James K. Koehler ◽  
Steven G. Reed ◽  
Joao S. Silva

As part of a larger study involving the co-infection of human monocyte cultures with HIV and protozoan parasites, electron microscopic observations were made on the course of HIV replication and infection in these cells. Although several ultrastructural studies of the cytopathology associated with HIV infection have appeared, few studies have shown the details of virus production in “normal,” human monocytes/macrophages, one of the natural targets of the virus, and suspected of being a locus of quiescent virus during its long latent period. In this report, we detail some of the interactions of developing virons with the membranes and organelles of the monocyte host.Peripheral blood monocytes were prepared from buffy coats (Portland Red Cross) by Percoll gradient centrifugation, followed by adherence to cover slips. 90-95% pure monocytes were cultured in RPMI with 5% non-activated human AB serum for four days and infected with 100 TCID50/ml of HIV-1 for four hours, washed and incubated in fresh medium for 14 days.


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