Label-Free Fluorescent Poly(amidoamine) Dendrimer for Traceable and Controlled Drug Delivery

Abstract

Poly(amidoamine) dendrimer (PAMAM) is well known for its high efficiency as a drug 3 delivery vehicle. However, the intrinsic cytotoxicity and lack of a detectable signal to facilitate 4 tracking have impeded its practical applications. Herein, we have developed a novel label-free 5 fluorescent and biocompatible PAMAM derivative by simple surface modification of PAMAM 6 using acetaldehyde. The modified PAMAM possessed a strong green fluorescence, which was 7 generated by the C=N bonds of the resulting Schiff Bases via n-π* transition, while the intrinsic 8 cytotoxicity of PAMAM was simultaneously ameliorated. Through further PEGylation, the 9 fluorescent PAMAM demonstrated excellent intracellular tracking in human melanoma 10 SKMEL28 cells. In addition, our PEGylated fluorescent PAMAM derivative achieved 11 enhanced loading and delivery efficiency of the anticancer drug doxorubicin (DOX) compared 12 to the original PAMAM. Importantly, the accelerated kinetics of DOX-encapsulated 13 fluorescent PAMAM nanocomposites in an acidic environment facilitated intracellular drug 14 release, demonstrating comparable cytotoxicity to that of the free-form doxorubicin 15 hydrochloride (DOX•HCl) against melanoma cells. Overall, our label free fluorescent 16 PAMAM derivative offers a new opportunity of traceable and controlled delivery for DOX and 17 other drugs of potential clinical importance.

A Robust Intrinsically Green Fluorescent Poly(Amidoamine) Dendrimer for Imaging and Traceable Central Nervous System Delivery in Zebrafish

“…Furthermore, the fluorescence intensity of fabricated FGP was pH-independent when tested in different pH (5.0, 6.0, and 7.2) solution ( Figure S3, Supporting Information), a critical feature for the applications in complex biological environments. [28] As measured by dynamic light scattering (DLS), the original FG5 had a size of 4.6 ± 1.5 nm, close to the theoretical value of PAMAM G5 [13] (5.4 nm; Figure 1D). After PEGylation, the size increased to 6.7 ± 1.1 nm, suggesting successful conjugation of PEG.…”

“…Furthermore, aggregation of hydrophobic fluorophores followed by self‐quenching and photo bleaching also highly influence their optical performance and hinder utility for in vivo applications. [ 11–13 ]…”

“…followed by self-quenching and photo bleaching also highly influence their optical performance and hinder utility for in vivo applications. [11][12][13] To address these limitations, several IF-PAMAMs have been designed, as exemplified by 1-(4-carbomethyoxy) pyrrolidoneterminated dendrimers and chemically oxidized hydroxylterminated PAMAM dendrimers. [12,14,15] However, these probes have only been tested in vitro without further validation in vivo.…”

Gene silencing-mediated immune checkpoint blockade for tumor therapy boosted by dendrimer-entrapped gold nanoparticles

“…to G5.NH 2 dendrimers was dissolved in water (7.69 mL), dropped into a G5.NH 2 dendrimer solution (50 mg, in 5 mL water), followed by stirring for 4 h according to Ref. [37]. Then, we dialyzed the reaction mixture through a membrane with a molecular weight cut-off (MWCO) of 5000 Da for three days (nine times, 2 L), and lyophilized the dialysis liquid to acquire the G5.…”

Are PAMAM dendrimers safe for ocular applications? -- Toxicological evaluation in ocular cells and intraocular tissues

“…2B). The high number of positive charges of the dense terminal amines of PAMAM interact with the negatively charged lipid bilayers of the cell membrane, which eventually leads to membrane disruption(21,22). At the same time, PAMAM showed a time-dependent cytotoxic effect.…”