In Situ Nanoparticle Self-Assembly for Combination Delivery of Therapeutics to Non-Small Cell Lung Cancer

Abstract

Chemotherapy often experiences several challenges including severe systemic toxicity and adverse effects. The combination chemotherapy arose as an effective clinical practice aimed at reducing doses of drugs to achieve synergistic actions with low toxicity. Our recent efforts demonstrated a synergistic therapeutic benefit of gambogic acid (GA) and gemcitabine (Gem) against lung cancer. However, simultaneous delivery of these two drugs at the tumor site is highly challenging. Therefore, the development of an injectable formulation that can effectively deliver both hydrophobic (GA) and hydrophilic (Gem) drugs in one formulation is a clinically unmet need. Herein, this study reports an in situ human serum albumin (HSA)-and tannic acid (TA)-mediated complexed GA and Gem nanoparticles (G−G@HTA NPs). G−G@HTA NP formation was confirmed by the particle size, Fourier transform infrared spectroscopy, and 1 H NMR spectroscopy. The superior therapeutic activity of G−G@HTA NPs was demonstrated by multiple in vitro functional assays. Additionally, G−G@HTA NPs revealed an obvious and precise targeting of tumors in vivo. The promoted and more synergistic anti-tumor efficacy of G−G@HTA NPs was attained than that of combined treatments and single drug treatments. These events have resulted in no apparent systemic and organ toxicities. Together, this study suggests that in situ HSA− TA-based combinatorial treatment strategy is a suitable approach for application in lung cancer treatment.

Indocyanine Green-based Glow Nanoparticles Probe for Cancer Imaging

“…Animals were housed in the animal house at the Cancer Research Building of University of Tennessee Health Science Center (Memphis, TN, USA) and animals had access to water and food ad libitum. The tumor xenografts on hind flanks of mice were established using breast cancer cell line (MDA-MB-231, 2×10 6 cells) according to our established protocol [32,39]. Three mice per group (ICG or ICG-Glow NPs) was randomly distributed and were treated with either 100 µg ICG solution or 100 µg equivalent ICG containing ICG-Glow NPs by intraperitoneal administration.…”

“…Three mice per group (ICG or ICG-Glow NPs) was randomly distributed and were treated with either 100 µg ICG solution or 100 µg equivalent ICG containing ICG-Glow NPs by intraperitoneal administration. Under anesthetic condition, mice were imaged at 3, 6, and 24 h by IVIS XRMS Imaging System (Caliper Life Sciences, Waltham, MA) [39,40]. After tumor targeting imaging, mice were sacrificed, and tumors were dissected and ex vivo quantification of fluorescence was taken by IVIS XRMS Imaging System.…”