<p>Antitumor Activity of Thermosensitive Hydrogels Packaging Gambogic Acid Nanoparticles and Tumor-Penetrating Peptide iRGD Against Gastric Cancer</p>

Abstract

Introduction: Gambogic acid (GA) is proved to have anti-tumor effects on gastric cancer. Due to poor solubility, non-specific biological distribution, toxicity to normal tissues and short half-life, it is hard to be applied into the clinic. To overcome these issues, we developed a thermosensitive and injectable hydrogel composed of hydroxypropyl cellulose, silk fibroin and glycerol, with short gelling time, good compatibility and sustained release, and demonstrated that the hydrogel packaged with gambogic acid nanoparticles (GA-NPs) and tumorpenetrating peptide iRGD could improve the anti-tumor activity. Methods: The Gelling time and micropore size of the hydrogels were regulated through different concentrations of glycerol. Controlled release characteristics of the hydrogels were evaluated with a real-time near-infrared fluorescence imaging system. Location of nanoparticles from different carriers was traced by confocal laser scanning microscopy. The in vivo antitumor activity of the hydrogels packaging GA-NPs and iRGD was evaluated by investigating tumor volume and tumor size. Results: The thermo-sensitive properties of hydrogels were characterized by 3-4 min, 37°C, when glycerol concentration was 20%. The hydrogels physically packaged with GA-NPs and iRGD showed higher fluorescence intensity than other groups. The in vivo study indicated that the co-administration of GA-NPs and iRGD by hydrogels had higher antitumor activity than the GA-loaded hydrogels and free GA combining with iRGD. Free GA group showed few antitumor effects. Compared with the control group, the body weight in other groups had no obvious change, and the count of leukocytes and hemoglobin was slightly decreased. Discussion: The hydrogel constructed iRGD and GA-NPs exerted an effective anti-tumor effect possibly due to retention effect, local administration and continuous sustained release of iRGD promoting the penetration of nanoparticles into a deep part of tumors. The delivery system showed little systemic toxicity and would provide a promising strategy to improve anti-gastric cancer efficacy.

<p>Gambogic Acid Inhibits the Progression of Gastric Cancer via circRNA_ASAP2/miR-33a-5p/CDK7 Axis</p>

“…Gambogic acid (GA), gotten from Garcinia hanburyi, is the major ingredient of gamboge. 3 Numerous studies indicated that GA acted as the suppressor of cancers, including GC. 3,4 For example, Wang et al indicated that GA could increase docetaxel sensitivity in GC cells.…”

“…3 Numerous studies indicated that GA acted as the suppressor of cancers, including GC. 3,4 For example, Wang et al indicated that GA could increase docetaxel sensitivity in GC cells. 5 Zou et al revealed that GA induced cell apoptosis together with chemotherapeutic agents in GC cells.…”

Influencing factors and strategies of enhancing nanoparticles into tumors in vivo

“…It was found that the absorption of MNPs by macrophages RAW264.7 was reduced to half of the original level 72 . In addition to PEG, modification with other chemicals (as shown in Table 1 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 ) can also extend the blood circulation time of NPs.…”

iRGD Peptide as a Tumor-Penetrating Enhancer for Tumor-Targeted Drug Delivery

“…Cellular uptake of doxorubicin-encapsulated iRGD-conjugated nanogels was also observed in B16 melanoma cells, with the alleviation of side effects caused by doxorubicin [ 125 ]. The iRGD-conjugated hydrogels of gambogic acid nanoparticles (GA-NPs) promoted the antitumor activity due to the enhanced penetration into tumor sites, ultimately leading to reduced tumor volume and a distinct anti-tumor effect [ 139 ].…”

“…Instead, a simple co-administration with iRGD improves drug efficacy, such as that of doxorubicin and nab-paclitaxel (Abraxane ® ). The iRGD moiety, via binding of the CendR motif and NRP-1, activates a bulk transport process that sweeps along compounds or therapeutic drugs present in blood [ 54 , 139 ]. Despite this report, there have been continuous attempts to maximize its effect by devising innovative vehicles through conjugation techniques.…”