Programmable Delivery of Synergistic Cancer Drug Combinations Using Bicompartmental Nanoparticles

Abstract

Delivery of multiple therapeutics has become a preferred method of treating cancer, albeit differences in the biodistribution and pharmacokinetic profiles of individual drugs pose challenges in effectively delivering synergistic drug combinations to and at the tumor site. Here, bicompartmental Janus nanoparticles comprised of domains are reported with distinct bulk properties that allow for independent drug loading and release. Programmable drug release can be triggered by a change in the pH value and depends upon the bulk properties of the polymers used in the respective compartments, rather than the molecular structures of the active agents. Bicompartmental nanoparticles delivering a synergistic combination of lapatinib and paclitaxel result in increased activity against HER2+ breast cancer cells. Surprisingly, the dual drug loaded particles also show significant efficacy toward triple negative breast cancer, even though this cancer model is unresponsive to lapatinib alone. The broad versatility of the nanoparticle platform allows for rapid exploration of a wide range of drug combinations where both their relative drug ratios and temporal release profiles can be optimized.

Acetalated dextran based nano- and microparticles: synthesis, fabrication, and therapeutic applications

“…5d). 50 The NPs were less than 200 nm, much smaller than the ones formulated in the previous setups. However, a non-volatile solvent (dimethylformamide, 30% v/v) was used in this study, making an unfavourably long drying (3 weeks) to remove all the solvents.…”

Multiple Targeted Self-Emulsifying Compound RGO Reveals Obvious Antitumor Potential in Hepatocellular Carcinoma

“…The molecular mechanisms involved in tumorigenesis are multi-facet and complex with tolerance to monotherapies easily generated [45]. Hence, combinatorial therapies are employed to maximize treatment e cacy [8]. Herein, RGO-SMEDDS was shown to have superior therapeutic e cacy against HCC both in vitro and in vivo.…”

“…This dose was 100 times that of the actual clinical dosage, indicating that RGO-SMEDDS has no obvious toxic side effects. The safety of RGO-SMEDDS may be attributed to the following: Rg3, GLP, and Oridonin are less toxic as natural drugs [74,75]; Synergistic effects among drugs reduce the unnecessary drug amount while still achieved equal e ciency [6,8]; SMEDDS improve the bioavailability of drugs [34,76].…”

“…Multidrug therapy is advantageous due to the effect on multiple signaling pathways simultaneously. The resultant anti-tumor effects can more effectively reduce drug resistance [6,[8][9][10][11]. In this study, we evaluated the anti-tumor effect and mechanism of a new self-emulsifying compound, RGO-SMEDDS.…”

Systemic delivery of a CXCR4-CXCL12 signaling inhibitor encapsulated in synthetic protein nanoparticles for glioma immunotherapy

“…To overcome this obstacle, we designed SPNPs that facilitate AMD3100 delivery to GBM. AMD3100-loaded SPNPs were prepared via electrohydrodynamic (EHD) jetting [47][48][49][50][51][52] . In brief, a dilute solution of human serum albumin (HAS), AMD3100, and a bifunctional OEG macromer (NHS-OEG-NHS, 2 kDa) is atomized and results in the preparation of well-defined nanoparticles (Figure 5A).…”