Oral Delivery of Gambogenic Acid by Functional Polydopamine Nanoparticles for Targeted Tumor Therapy

Abstract

To enhance the water solubility, oral bioavailability, and tumor targeting of gambogenic acid (GNA), polydopamine nanoparticles (PDA NPs) were prepared to encapsulate and stabilize GNA surface modified by folic acid (FA) and then coated with sodium alginate (GNA@PDA-FA SA NPs) to achieve an antitumor effect by oral administration. GNA@PDA-FA SA NPs exhibited in vitro pH-sensitive release behavior. In vitro cell studies manifested that GNA@PDA-FA NPs had higher cytotoxicity to 4T1 cells compared with raw GNA (IC 50 = 2.58 μM vs 7.57 μM). After being modified with FA, GNA@PDA-FA NPs were taken up easily by 4T1 cells. In vivo studies demonstrated that the area under the curve (AUC 0→∞ ) of the plasma drug concentration−time of GNA@ PDA-FA SA NPs was 2.97-fold higher than that of raw GNA, along with improving drug distribution in the liver, lung, and kidney tissues. In vivo anti-tumor experiments, GNA@PDA-FA SA NPs significantly inhibited the growth of breast tumors in the 4T1 xenograft breast cancer model via oral administration without obvious toxicity on major organs. Our studies indicated that the GNA@PDA-FA SA NPs modified with FA and coated with SA were a promising drug delivery system for targeting tumor therapy via oral administration.

Unveiling Gambogenic Acid as a Promising Antitumor Compound: A Review

“…Various studies have confirmed that GNA has antitumor potential in vivo. GNA can counteract tumor growth in vivo in various tumor mouse models, such as lung cancer [37], breast cancer [55], and multiple myeloma [33] (▶ Table 2). These experiments mostly utilize xenograft models, among which the patient-derived tumor xenograft (PDX) model has emerged as the most trustworthy in vivo human cancer model due to its ability to preserve the features of the original patient tumor, such as gene expression profiles and treatment responses [56].…”

“…In addition, Wang et al [55] encapsulated and stabilized GNA in polydopamine nanoparticles (PDA-NPs), which further modified the surface of the particles with folic acid (FA) and finally coated it with sodium alginate (SA) to form GNA@PDA-FA SA NPs, where FA was used as an active targeting ligand due to its high specific binding with folate receptors, making it easily taken up by 4 T1 cells, while SA was used to prevent the modified nanoparticles from being degraded by the gastric fluid when taken orally. Compared with GNA, GNA@PDA-FA SA NPs exhibited a higher anti-breast cancer therapeutic effect in vivo and in vitro.…”

Polymer nano-systems for the encapsulation and delivery of active biomacromolecular therapeutic agents

“…178 In another example, polydopamine nanoparticles loaded with gambogenic acid, an anti-cancer drug, showed that after oral administration in mice, the polymer DDS increased the plasma drug concentration almost 3 times without apparent toxicity to the major organs. 179 One of the major challenges associated with oral delivery is the transit through the gastrointestinal tract and the very acidic pH of this environment, which also contain a complex enzymatic system. Protecting the sensitive structure of the biomacromolecular therapeutic agent, such as genetic material, under such harsh conditions is difficult.…”

Melanin-like nanoparticles: advances in surface modification and tumour photothermal therapy

“…Current conventional chemotherapeutic drugs lack targeting and may be toxic to normal cells while killing cancer cells, resulting in intolerable side effects. Several targeting ligands, including nuclear adaptors (AS1411 and peptides) [ 127 ], small molecules (folic acid) [ 128 ], and epidermal growth factor (EGFR) [ 129 ], can be modified with polyethylene glycol chains (PEG) at the ends and grafted onto the surface of PDA under mild conditions due to the high responsiveness of PDA. (FR), which is overexpressed in many cancer cells, was used as an active targeting ligand in a nanoscale drug delivery system and modified on the surface of PDA-coated gambogenic acid (GNA) nanoparticles via Michael addition reactions ( Fig.…”

“…B Schematic representation of the preparation of ZP-DOX-FA.Republished from Ref. [ 129 , 130 ]. under the terms of the Creative Commons Attribution Licence (CC BY) ( http://creativecommons.org/licences/by/4.0/ ) …”