Nanostructured lipid carriers as co-delivery systems for cancer therapy: Prospects and challenges

Cancer combination therapy is widely used to address tumor heterogeneity, multidrug resistance, and dose-limiting toxicities associated with conventional monotherapy. However, the clinical benefits of free-drug combinations are often compromised by mismatched pharmacokinetics, inconsistent intratumoral drug ratios, and poor solubility or stability of individual agents. Nanostructured lipid carriers (NLCs), composed of a solid-liquid lipid matrix, have emerged as a biocompatible nanoplatform capable of overcoming these limitations through high drug-loading capacity, improved colloidal stability, and tunable release behavior. This review aims to summarize the role of NLCs as co-delivery systems for cancer therapy. A literature search was conducted across databases to identify studies reporting NLC-based co-delivery strategies for anticancer applications. By enabling the co-encapsulation of multiple cargos inside a single carrier, NLCs facilitate synergistic interactions, maintain synchronized biodistribution, and enhance intracellular accumulation at tumor sites. These attributes support the co-delivery of diverse therapeutic modalities, including chemotherapeutics, genetic materials, and stimuli-responsive particles such as photodynamic, photothermal, and magnetic hyperthermia agents. The review briefly examines the structural features, formulation considerations, and preparation techniques of NLCs, followed by discussions of the rationales for co-loading strategy and representative applications across various cancer types. Challenges related to formulation complexity, manufacturing scalability, safety, and regulatory translation remain important considerations, whereas advances in rational formulation design and data-driven development strategies may accelerate the clinical translation of NLC-based co-delivery systems and expand their potential in cancer therapy.