Self-assembly drug conjugates for anticancer treatment

Abstract

Please cite this article as: Fumagalli, G., Marucci, C., Christodoulou, M.S., Stella, B., Dosio, F., Passarella, D.,Self-assembly drug conjugates for anticancer treatment, Drug Discovery Today (2016), http://dx.doi.org/10.1016/j.drudis. 2016.06.018 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t Keywords: Self-assembly; drug conjugate; nanoparticle. Self-assembly drug conjugates for anticancer treatmentTeaser: In this review we summarize the recent advances in nanoparticles obtained by self-assembly drug conjugates, a useful tool to improve drug delivery of anticancer compounds. Page 4 of 25A c c e p t e d M a n u s c r i p tSelf-assembly drug conjugate preparation is a promising approach to improve activity and penetration through physiological barriers of potent small molecules, as well as to reduce any side effects. Drug conjugates can self-assemble in water to form nanoparticles (NPs) that offer several advantages because: (i) they are easy to obtain; (ii) they can reach high local drug concentration in tumor tissues; and (iii) they can reduce the side effects of drugs. All these factors improve drug pharmacokinetic properties. Here, we have reviewed the scope of nanotechnology-based self-assembly drug delivery approaches focusing on prodrugs able to form NPs by self-assembly; we have also summarized the current perspective and challenges facing the successful treatment of cancer.

Stereochemistry and complete 1H and 13C NMR signal assignment of C‐20‐oxime derivatives of posterone 2,3‐acetonide in solution state

“…Self‐assembling nanoparticles provide a promising novel approach against cancer . These can be prepared by functionalizing a potential antitumor agent with a long lipophilic side‐chain through functional group(s) hydrolysable in a biological environment (e.g., ester), which will make them working as prodrugs once released.…”

Conjugation of squalene to gemcitabine as unique approach exploiting endogenous lipoproteins for drug delivery

“…In this context, we have developed an original approach relying on the introduction of squalene (SQ), a natural triterpene and precursor of the cholesterol's biosynthesis, as a biocompatible material for drug delivery purposes. Squalene has been used as a building block for the synthesis of SQ-drug bioconjugates, which demonstrated the ability to self-assemble in aqueous medium in the form of nanoparticles (NPs), without the need of any other transporter material678. The bioconjugates obtained by the covalent linkage of SQ to gemcitabine (SQGem) resulted in the spontaneous formation of NPs in water, with a diameter of ∼100–200 nm and high drug loading (∼40%)9.…”

Novel reduction‐sensitive micellar nanoparticles assembled from Rituximab–doxorubicin conjugates as smart and intuitive drug delivery systems for the treatment of non‐Hodgkin's lymphoma

“…Recent years, nanotechnology has opened new perspectives for biological and biomedical applications to improve the selective delivery and release of anticancer agents to tumor tissues and cells, among which the use of drug conjugates to obtain nanoparticles by self‐assembly has gained considerable attention. The self‐assembly of drug conjugates can be obtained with different methods and conditions but the key role of the amphilicity of the components is often fundamental . In the past decades, drug conjugate‐based polymeric micelles (PMs) are one of the most studied nanovehicles in diagnosing and treating malignant tumors, which are constituted by an inner hydrophobic core (poorly aqueous‐soluble drugs) and an outer hydrophilic corona that helps to protect and stabilize the encapsulated drugs .…”

“…The self‐assembly of drug conjugates can be obtained with different methods and conditions but the key role of the amphilicity of the components is often fundamental . In the past decades, drug conjugate‐based polymeric micelles (PMs) are one of the most studied nanovehicles in diagnosing and treating malignant tumors, which are constituted by an inner hydrophobic core (poorly aqueous‐soluble drugs) and an outer hydrophilic corona that helps to protect and stabilize the encapsulated drugs . Currently, there are two formulations that have respectively reached Phase II (NK911) and Phase III (SP1049C) clinical trials and that are worth describing .…”

“…[16,17] Currently, there are two formulations that have respectively reached Phase II (NK911) and Phase III (SP1049C) clinical trials and that are worth describing. [16] However, there is no report on the study of antibody-drug conjugate-based nanoparticles in the treatment of malignant tumors. In this study, a newly designed ADC was synthesized by conjugating hydrophobic cytotoxic agents (doxorubicin, DOX) to hydrosoluble Fragments of anti-CD20 mAbs (rituximab, RTX) via a reduction-responsive linker, disulfide bond 3-(2-pyridyldithio) propionyl hydrazide (PDPH).…”