Design of riboflavin-presenting PAMAM dendrimers as a new nanoplatform for cancer-targeted delivery

Abstract

This communication describes the synthesis and in vitro biological evaluation of novel generation 5 PAMAM dendrimers conjugated with riboflavin as a targeting ligand. Cell-based experiments demonstrated that a dendrimer conjugated with riboflavin is able to undergo cellular binding and uptake in KB cells, and when the dendrimer is also conjugated with methotrexate, the riboflavin dendrimer conjugate can potently inhibit cell growth.

Photoacoustic imaging of tumor targeting with riboflavin-functionalized theranostic nanocarriers

“…19,27,28 This feature was demonstrated in several preclinical studies with a variety of used carriers -from iron oxide nanoparticles to polymers. 17,18,22,27 In our previous study, we validated the efficacy of cancer and endothelial cell targeting in vitro and in vivo by RF amphiphiles inserted into a liposome formulation. 28 However, the applied combined microcomputed tomography/ fluorescence molecular tomography imaging platform used for these studies has a limited translational potential.…”

“…In this context, riboflavin (RF)-based targeting represents a promising approach for cell labeling, 17,18 tumor contrast enhancement, 19 and cell-specific drug delivery. [20][21][22] Due to its involvement in cell growth and development, RF is of high demand in metabolically active cells such as various malignant (eg, breast, prostate cancer, and hepatocellular carcinoma) and rapidly growing endothelial cells. [23][24][25][26] Thus, a major argument for using RF as a ligand for targeted drug delivery is that it targets both cancerous cells and the tumor stroma including the angiogenic endothelium.…”

Bioconjugates of PAMAM dendrimers with trans-retinal, pyridoxal, and pyridoxal phosphate

“…[2][3][4][5][6][7][8][9][10] On the other hand, full-generation PAMAM dendrimers have surface amine groups (32 amine groups in the third-generation PAMAM dendrimer, G3), offering an easy route for formation of conjugates with drugs. [11][12][13][14][15][16][17][18][19][20][21] Due to the relatively low toxicity of PAMAM dendrimers, [22][23][24][25] they are frequently used as transdermal diffusion promoters. 26 In previous studies, we have used PAMAM dendrimers as carriers for 8-methoxypsoralen, the photosensitizer used in psoralen and ultraviolet light A therapy (PUVA), 4 riboflavin, 5 and vitamin C. 27 In all these cases, the PAMAM dendrimers formed host-guest complexes with 8-methoxypsoralen, vitamin B 2 and vitamin C, thereby modifying the transdermal flux of the guest molecule.…”

“…Another approach to influencing the rate of transdermal diffusion is based on covalent binding of a prodrug and using such bioconjugates as a platform for introducing the drug into skin tissue. In terms of potential dermatological application, bioconjugates of folate, 11 biotin, 12 riboflavin, 13 cholic acid, 14 and phosphorylcholine 15 have been synthesized and tested as membrane permeability enhancers, increasing the cellular uptake of the drug. Here we report on bioconjugates obtained from third-generation PAMAM dendrimers, retinal ([Ret] vitamin A), pyridoxal ([Pyr] vitamin B 6 ), or pyridoxal phosphate ([PLP] metabolically active coenzyme of vitamin B 6 ).…”

Dermatological Application of PAMAM – Vitamin Bioconjugates and Host-Guest Complexes – Vitamin C Case Study

“…Thus, the PAMAM bioconjugates with drugs synthesized and tested in vitro so far are the one with methotrexate and folate ( (Wiwattanapatapee et al, 2003), and especially important for skin treatment phosphorylcholine (Jia et al, 2011), cholic acid (Zhang et al, 2011), biotin (Yang et al, 2009), and riboflavin (Thomas et al, 2010). Similar studies are currently being performed in our laboratory to clarify the skin penetration of vitamins supported by PAMAM dendrimers.…”