<p>Transferrin Conjugated pH- and Redox-Responsive Poly(Amidoamine) Dendrimer Conjugate as an Efficient Drug Delivery Carrier for Cancer Therapy</p>

Abstract

Introduction: A multifunctional redox-and pH-responsive polymeric drug delivery system is designed and investigated for targeted anticancer drug delivery to liver cancer. Methods: The nanocarrier (His-PAMAM-ss-PEG-Tf, HP-ss-PEG-Tf) is constructed based on generation 4 polyamidoamine dendrimer (G4 PAMAM). Optimized amount of histidine (His) residues is grafted on the surface of PAMAM to obtain enhanced pH-sensitivity and proton-buffering capacity. Disulfide bonds (ss) are introduced between PAMAM and PEG to reach accelerated intracellular drug release. Transferrin (Tf) was applied to achieve active tumor targeting. Doxorubicin (DOX) is loaded in the hydrophobic cavity of the nanocarrier to exert its anti-tumor effect. Results: The results obtained from in vitro and in vivo evaluation indicate that HP-ss-PEG-Tf/DOX complex has pH and redox dual-sensitive properties, and exhibit higher cellular uptake and cytotoxicity than the other control groups. Flow cytometry and confocal microscopy display internalization of HP-ss-PEG-Tf/DOX via clathrin mediated endocytosis and effective endosomal escape in HepG2 cancer cells. Additionally, cyanine 7 labeled HP-ss-PEG-Tf conjugate could quickly accumulate in the HepG2 tumor. Remarkably, HP-ss-PEG-Tf/DOX present superior anticancer activity, enhanced apoptotic activity and lower heart and kidney toxicity in vivo. Discussion: Thus, HP-ss-PEG-Tf is proved to be a promising candidate for effective targeting delivery of DOX into the tumor.

Combinational Chemoimmunotherapy for Breast Cancer by Codelivery of Doxorubicin and PD-L1 siRNA Using a PAMAM-Incorporated Liposomal Nanoplatform

“…Low temperatures (4 °C) usually inhibit the activity of various enzymes, resulting in reduced mitochondrial energy production and thereby reducing cellular uptake. 36,41 After treatment with hypertonic sucrose and chlorpromazine, the cellular uptake of siPD-L1@ PM/DOX@LPs was reduced by 51 and 54%, respectively. Both of these substances disrupt internalization via clathrincoated pits.…”

“…Poly (amido amine) (PAMAM) dendrimer has proven to be an efficient gene carrier. PAMAM is a polycation that can be used to condense siRNA into nanoscale complexes to prevent nuclease degradation. ,− However, PAMAM is cytotoxic and can be quickly cleared from plasma when administered intravenously . Therefore, in the present study, we combined the unique advantages of the two vectors to design a “simple but robust” multifunctional liposomal nanocarrier that contains a pH-sensitive LP shell and a dendritic PAMAM core for codelivery of siPD-L1 and DOX (siPD-L1@PM/DOX/LPs, Scheme A).…”

Baseline and time‐updated factors in preclinical development of anionic dendrimers as successful anti‐HIV‐1 vaginal microbicides

“…Dendrimers offer unique opportunities as biological agents, especially as carriers for chemical drugs or peptides (Hu et al, 2020; Sepulveda‐Crespo et al, 2016; Shcharbin et al, 2020), as powerful tool for gene silencing (Dong et al, 2020; Ellert‐Miklaszewska et al, 2019), as antibacterial agents (Abd‐El‐Aziz et al, 2020; Alfei & Schito, 2020; Mlynarczyk et al, 2020; Sanz Del Olmo et al, 2020), as well as to have intrinsic antiviral activities, such as against HIV‐1 (Cena‐Diez et al, 2017; Guerrero‐Beltran et al, 2019; Rodriguez‐Izquierdo et al, 2019; Sepulveda‐Crespo, Serramia, et al, 2015; Vacas‐Cordoba et al, 2016), HIV‐2 (Briz et al, 2015), HSV‐2 (Cena‐Diez, Vacas‐Cordoba, et al, 2016; Guerrero‐Beltran et al, 2020; Rodriguez‐Izquierdo et al, 2020), HCV (Javadi et al, 2019; San Anselmo et al, 2020; Sepulveda‐Crespo, Jimenez, et al, 2017), HPV (Donalisio et al, 2010), influenza virus (Farabi et al, 2020; Hatano et al, 2014), respiratory syncytial virus (RSV) (Gazumyan et al, 2000), or Middle East respiratory syndrome coronavirus (MERS‐CoV) (Kandeel et al, 2020).…”

Smart Nanomaterials for Biomedical Applications—A Review

“…As the expectation is to "take out two targets with one shot", researchers have just depicted the arising idea to engineer "intelligent" nanosystems for simultaneously realizing diagnosis and therapy. These nanosystems used in fighting against cancer are based on nanoplatforms which could efficiently co-entrap photosensitizers and chemotherapy, dendrimers, functional nanocarriers, drug-loaded nan-aggregates, liposomes, hybrid nanoparticles, and nanogels for "on-demand" anticancer drug delivery [137][138][139][140][141][142][143][144][145][146][147][148][149]. All of these systems are composed of multi-stimuli-responsive versatile materials, which enable them to ensure the expected requirements.…”