In part I of this review, the authors showed how poly(amidoamine) (PAMAM)-based dendrimers can be considered as promising delivering platforms for siRNA therapeutics. This is by virtue of their precise and unique multivalent molecular architecture, characterized by uniform branching units and a plethora of surface groups amenable to effective siRNA binding and delivery to e.g., cancer cells. However, the successful clinical translation of dendrimer-based nanovectors requires considerable amounts of good manufacturing practice (GMP) compounds in order to conform to the guidelines recommended by the relevant authorizing agencies. Large-scale GMP-standard high-generation dendrimer production is technically very challenging. Therefore, in this second part of the review, the authors present the development of PAMAM-based amphiphilic dendrons, that are able to auto-organize themselves into nanosized micelles which ultimately outperform their covalent dendrimer counterparts in in vitro and in vivo gene silencing.
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http://dx.doi.org/10.3390/pharmaceutics11070324 | DOI Listing |
Biotechnol J
November 2024
Medical Biotechnology, Life Sciences, TUBITAK Marmara Research Center, Kocaeli, Türkiye.
A promising approach to treat colorectal cancer (CRC) involves combining chemotherapy, epigenetics, and gene therapy to combat drug resistance. Multifunctional nanocarriers have emerged as a valuable tool for targeted CRC therapy. By delivering multiple treatments directly to cancer cells, these nanocarriers offer the potential for improved outcomes and reduced side effects.
View Article and Find Full Text PDFJ Am Chem Soc
October 2024
School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China.
Polymers (Basel)
July 2024
Interdisciplinary Institute for Medical Engineering, Fuzhou University, Fuzhou 350108, China.
Glioma is the most common primary intracranial tumor, which is formed by the malignant transformation of glial cells in the brain and spinal cord. It has the characteristics of high incidence, high recurrence rate, high mortality and low cure rate. The treatments for glioma include surgical removal, chemotherapy and radiotherapy.
View Article and Find Full Text PDFOrg Biomol Chem
October 2023
Departamento de Fisiología, Facultad de Ciencias Biológicas, Universidad de Concepción, Barrio Universitario S/N, Concepción, Chile.
Surface-modified PAMAM dendrimers have important applications in drug delivery, yet a gap remains about the role that surface functionalization plays on their cell internalization capacity. We examined the cell internalization kinetics of PAMAM dendrimers that were surface-modified with acetyl, folate and poly(ethylene glycol), as model functional groups differing in size, charge, and chemical functionality. Dendrimers with 25% functionalization were internalized by HEK cells, but with slower rates and lower maximum uptakes than the native dendrimer between 1-6 h of incubation.
View Article and Find Full Text PDFBioconjug Chem
June 2023
Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy.
Polyamidoamine (PAMAM) dendrimers are among the most studied cationic polymers as non-viral gene delivery vectors. However, an "ideal" PAMAM-based gene delivery vector is still missing due to the high manufacturing costs and non-negligible cytotoxicity associated with the use of high-generation dendrimers, whereas low-generation dendrimers are far from displaying efficient gene transfection. In order to cover this gap in the literature, in this study, we propose the functionalization of the outer primary amines of PAMAM G2 and PAMAM G4 with building blocks bearing fluorinated moieties along with a guanidino functional group.
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