Recent Advances in Engineering of Lipid Drug Conjugates for Cancer Therapy

Cancer chemotherapy has witnessed the translation of a good number of lipid-based formulations to the clinic based on drug encapsulation strategies. Toxicities associated with the release of anticancer drugs in systemic circulation and the usage of toxic excipients in these formulations along with poor efficacy, reducing blood circulation time and ineffective tumor-targeting ability, are responsible for poor success in patient survival. However, recent advances in bioconjugation strategies for engineering of lipid drug conjugates uplifted the physicochemical, pharmacokinetic/biodistribution properties, and antitumor activities of anticancer drugs with reduced toxicity in preclinical models as compared to traditional lipid formulations. Conjugation of the anticancer drugs to amphiphilic lipid molecules allows the sustained release of the drug under perfect stimuli conditions and their amphiphilic nature helps in formation of self-assembled nanoparticles that can easily be targeted at the tumor site. In this Review, we present recent advances in the emerging class of lipid drug conjugates (LDCs) for cancer therapy focusing on their design, tunable drug release at target sites, pharmacokinetics, antitumor activity, and toxicology, and provide future directions for their translation into the clinic.