Exploration of the Natural Active Small-Molecule Drug-Loading Process and Highly Efficient Synergistic Antitumor Efficacy

Abstract

The development and application of nano-drug carriers might provide an excellent opportunity for cancer therapy. However, it is still an important challenge to realize the regulation and control of drug loading by analyzing the assembly process of carrier-loaded drugs. Herein, we show a “self-contained bioactive nanocarrier” system, which is prepared from ursolic acid, one of the very promising biologically active natural products with self-assembly properties. The study decrypts the assembly process of drug-carrier interaction and achieves the regulation of drug loading by controlling the interaction force. This nanocarrier highlights the unique advantages of active natural products in therapeutic efficacy and health benefits. In antitumor experiments, the carrier and drug demonstrated synergistic therapeutic efficacy. Furthermore, the nanocarrier is biosafe and capable of reducing the risk of liver damage induced by chemotherapeutics through the upregulation of key antioxidant pathways. Taken together, this “self-contained bioactive nanocarrier” system makes up for the drawback that conventional nanocarriers have no therapeutic efficacy and health benefits and eliminates the trouble of the toxic side effects associated with chemotherapy agents and the additional toxicity caused by long-term use of nanocarriers.

Nanoformulations of Ursolic Acid: A Modern Natural Anticancer Molecule

“…The half-life of UA-PTX nanoparticles was significantly longer in vivo , about six times that of PTX alone. In addition, UA and PTX were observed to block MCF-7 tumor cell proliferation and induce apoptosis through different mechanisms, respectively, both of which had synergistic anti-tumor effect and reached a tumor inhibition rate of 90% ( Wang et al, 2020b ).…”

Reduced Thiol Compounds – Induced Biosensing, Bioimaging Analysis and Targeted Delivery

“…In addition to the nano drug delivery carriers, some small molecular carriers for drug delivery or prodrugs have also received widespread attention. The most widely used small molecular drug carriers include light‐cross‐linked enediyne micelle, [79‐80] natural active ursolic acid [81] and so on. Furthermore, one of the advantages of small‐molecule prodrugs is the potential for a high drug content, especially for amphiphilic drug−drug conjugates, in which one drug acts as the promoiety of the other [82‐84] .…”

Quantitative self-assembly of pure drug cocktails as injectable nanomedicines for synergistic drug delivery and cancer therapy

“…Therefore, self-deliverable systems assembled from single or multiple parent drugs could hold great potential for clinical translation due to the simplicity and feasibility in nanoparticle preparation 18 , 19 . Leveraging noncovalent interactions, some chemo drugs were capable of self-associating to form water-soluble nanoassemblies 20 - 22 . For instance, amphiphilic doxorubicin (DOX) were reported to assemble with hydrophobic agents (e.g., 10-hydroxycamptothecin and celastrol) into hybrid nanoparticles driven by π-π stacking and hydrophobic interactions, enabling intravenous injection of drug combinations 23 , 24 .…”