Table 6 Dendrimer based anti-GBM drug delivery system
Drug | Composite | Modification | Detail | Result |
|---|---|---|---|---|
Celecoxib (CXB) [169] | CXB@G3BC31 | Biotinylated third generation of the poly (amidoamine) dendrimer was substituted with 31 CXB residues | The cellular uptake, proliferation, migration and apoptosis were assessed in U-118 cells Model organism nematode Caenorhabditis elegans was used in toxicological studies | Cellular accumulation of dendrimer NPs in the lysosomes of tumor cells Up-regulated COX-2 level and cell cycle arrest Anti-tumor effect in vitro |
Arsenic trioxide (ATO) [170] | ATO@cRGD@mPEG@PAMAM | cRGD can bind to αvβ3 integrin peptides and combine with the integrin receptors on BBB | Cellular uptake, hemolytic toxicity and cytotoxicity were detected in C6 cells Intracellular disposition and BBB penetration were assessed Therapeutic efficacy was evaluated in Wistar rats model | Enhanced BBB penetration and intracellular disposition Cell cycle perturbations in G2/M phase Excellent therapeutic effect in vitro/vivo |
TRAIL [171] | TRAIL@Tf@PAMAM | Transferrin (Tf) receptor were overexpressed on BBB and utilized for facilitating brain targeting | Cellular uptake and apoptosis were determined in C6 cells Tumor xenografted SD rat model was established MRI imaging was utilized to monitor therapeutic effect | Accumulated NPs in brain tumor site Induced cell apoptosis Prolonged mean survival time and decreased tumor volume |
Rapamycin (RAPA) [172] | RAPA@ PAMAMOH | Hydroxyl PAMAM dendrimers (PAMAMOH) had the unique ability to target activated microglia | BV2 microglia were activated with IFNγ for inflammation analysis Anti-proliferative activity in GL261 cells was detected by MTT assay Systemic toxicity and anti-tumor evaluation were completed in C57BL/6 orthotopic mice model | Ablation and repolarization of TAMs Augmented anti-proliferative and tumor specificity properties in vitro Improved therapeutic efficacy in vivo |
Doxorubicin [173] | DOX@Borneol@ANG-2@PAMAM | Angiopep-2 could specifically target LPR on BBB surface Borneol promoted the permeation of drugs across BBB and enhanced their distribution in the brain tissue | Cellular uptake and intracellular disposition were detected through LSCM in HBMEC cells BBB penetration model was established In vitro cytotoxicity on HBMEC and C6 cells were evaluated | Sustained pH-sensitive DOX release Enhanced cytotoxicity and BBB penetration Promoted tumor specific NPs uptake level |