A carbohydrate mimetic peptide modified size-shrinkable micelle nanocluster for anti-tumor targeting and penetrating drug delivery.

Abstract

PURPOSE:

To deliver the chemotherapeutics through the nanoparticles, the delivery system should accumulate at the tumor site first and then penetrate through the interstitium into the interior. The specific tumor-targeting pathway mediated via the receptor-ligand binding could achieve the desirable accumulation of nanoparticles, and the nanoparticles with smaller sizes were required for penetration.

METHODS AND MATERIALS:

We constructed a size-shrinkable nanocluster modified with a tumor-targeting motif IF-7 (IF-7-MNC) based on a pH-sensitive framework which could be disintegrated in an acid environment to release the micelles aggregated inside. The micelles were constructed by amphiphilic block copolymers PEG-PLA to encapsulate paclitaxel (PTX), while the cross-linked framework consisting of TPGS-PEI was used as a net to gather and release micelles. This nanoplatform could specifically bind with the tumor receptor Annexin A1 through the ligand IF-7 and then shrunk into small micelles with a desirable size for penetration.

CONCLUSION:

IF-7-MNC of 112.27±6.81 nm could shrink into micelles in PBS (0.01 M, pH 5.0) with sizes of 14.89±0.32 nm. The cellular-uptake results showed that IF-7-MNC could be significantly internalized by A549 cells and HUVEC cells, while the penetration of IF-7-MNC could be more prominent into the 3D-tumor spheroids compared with that of MNC. The biodistribution results displayed that the fluorescence of IF-7-MNC in the tumor site at 24 hrs was 4.5-fold stronger than that of MNC. The results of anti-tumor growth demonstrated that IF-7-MNC was more favorable for the tumor therapy than MNC, where the inhibitory rate of tumor growth was 88.29% in the PTX-loaded IF-7-MNC (IF-7-PMNC) treated group, significantly greater than PMNC treatment group (p<0.05).

• Authors: Qinyue Chen, Huihui Liang, Yali Sun, Yiting Chen, Wenxiu He, Xiaoling Fang, Xianyi Sha, Jinming Li
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 14 Pg. 7339-7352 ( 2019) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 31686810 (Publication Type: Journal Article)
• Copyright: © 2019 Chen et al.

Chemical References

• Antineoplastic Agents
• Carbohydrates
• Micelles
• Peptides
• monomethoxypolyethyleneglycol-polylactide block copolymer
• Polyethylene Glycols
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Carbohydrates (chemistry)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Delivery Systems
• Drug Liberation
• Endocytosis
• Humans
• Hydrogen-Ion Concentration
• Inhibitory Concentration 50
• Male
• Mice, Inbred BALB C
• Mice, Nude
• Micelles
• Nanoparticles (chemistry, ultrastructure)
• Neoplasms (drug therapy)
• Paclitaxel (pharmacology, therapeutic use)
• Particle Size
• Peptides (chemistry)
• Polyethylene Glycols
• Spheroids, Cellular (drug effects, metabolism)
• Static Electricity
• Tissue Distribution