Combination of Small Molecule Prodrug and Nanodrug Delivery: Amphiphilic Drug–Drug Conjugate for Cancer Therapy

Abstract

All drugs for cancer therapy face several transportation barriers on their tortuous journey to the action sites. To overcome these barriers, an effective drug delivery system for cancer therapy is imperative. Here, we develop a drug self-delivery system for cancer therapy, in which anticancer drugs can be delivered by themselves without any carriers. To demonstrate this unique approach, an amphiphilic drug-drug conjugate (ADDC) has been synthesized from the hydrophilic anticancer drug irinotecan (Ir) and the hydrophobic anticancer drug chlorambucil (Cb) via a hydrolyzable ester linkage. The amphiphilic Ir-Cb conjugate self-assembles into nanoparticles in water and exhibits longer blood retention half-life compared with the free drugs, which facilitates the accumulation of drugs in tumor tissues and promotes their cellular uptake. A benefit of the nanoscale characteristics of the Ir-Cb ADDC nanoparticles is that the multidrug resistance (MDR) of tumor cells can be overcome efficiently. After cellular internalization, the ester bond between hydrophilic and hydrophobic drugs undergoes hydrolysis to release free Ir and Cb, resulting in an excellent anticancer activity in vitro and in vivo.

High drug-loading nanomedicines: progress, current status, and prospects

“…This class of dual-drugloaded nanomedicines has the advantages of ultrahigh drugloading content and synergistic combination chemotherapy because of its inherent nature. This strategy, which was first proposed by Huang et al, 201 is considered an excellent candidate for the fabrication of dual-drug synergistic therapy nanomedicines with high and fixed drug loading. Two methods are proposed under this strategy.…”

Multifunctional upconversion–nanoparticles–trismethylpyridylporphyrin–fullerene nanocomposite: a near-infrared light-triggered theranostic platform for imaging-guided photodynamic therapy

“…1-3 Specifically, phototriggered theranostics, combining phototherapies (for example, photodynamic, 4,5 photothermal, 6,7 and phototriggered chemo 8,9 / gene therapy 10 ) with real-time photodiagnostics (for example, bioluminescence, 11 fluorescence, 12,13 and photoacoustic imaging 14,15 ) have been actively pursued due to the advantages of spatiotemporal selectivity, non-ionizing radiation and specificity for disease destruction. Among them, near-infrared (NIR) light-triggered photodynamic theranostics, in which nanoparticles are used as photodynamic therapy (PDT) agents, have recently been receiving much attention due to deep penetration and simultaneous generation of reactive oxygen species (ROS) upon the NIR light irradiation, leading to ablation of cancer cells as a result.…”

Drug‐Bearing Supramolecular MMP Inhibitor Nanofibers for Inhibition of Metastasis and Growth of Liver Cancer

“…First, the critical aggregation concentration (CAC) was determined using pyrene as a fluorescent probe 18. According to the curve of the fluorescent intensity ratio ( I 1 / I 3 ) of pyrene versus DOX–KGFRWR concentration in water, the CAC value for DOX–KGFRWR was ≈50 × 10 −6 m , indicating that DOX–KGFRWR molecules start to aggregate into nanoparticles at concentrations greater than 50 × 10 −6 m (Figure S4, Supporting Information).…”