Cancer continues to be a prominent fatal health issue worldwide, driving the urgent need for more effective treatment strategies. The pressing demand has sparked significant interest in the development of advanced drug delivery systems for chemotherapeutics. The advent of nanotechnology offers a groundbreaking approach, presenting a promising pathway to revolutionize cancer treatment and improve patient outcomes. Nanomedicine-based drug delivery systems have demonstrated the capability of improving the pharmacokinetic properties and accumulation of chemotherapeutic agents in cancer sites while minimizing the adverse side effects. Despite these advantages, most NDDSs exhibit only limited improvement in cancer treatment during clinical trials. The recent development of magnetic nanoparticles (MNPs) for biomedical applications has revealed a potential opportunity to further enhance the performance of NDDSs. The magnetic properties of MNPs can be utilized to increase the targeting capabilities of NDDSs, improve the controlled release of chemotherapeutic agents, and weaken the chemoresistance of tumors with magnetic hyperthermia. In this review, we will explore recent advancements in research for NDDSs for oncology applications, how MNPs and their properties can augment the capabilities of NDDSs when complexed with them and emphasize the challenges and safety concerns of incorporating these systems into cancer treatment.

We present Jammed Interconnected Bilayer Emulsions (JIBEs) as a class of tissue-like materials with macroscopic scalability and rapid fabrication, comprising millions to billions of bilayer-separated aqueous compartments. These materials closely mimic the organizational structure and properties of biological tissues. Our rapid self-assembly method for producing JIBEs generates milliliter- to deciliter-scale volumes within minutes representing over 10,000-fold improvement in the fabrication speed of droplet-based artificial tissues compared to existing droplet-based methods, enabling the creation of a truly macroscopic material. The method is highly adaptable to a wide range of amphiphiles, including lipids and block-copolymers, providing flexibility in tailoring JIBEs for diverse applications. The jammed architecture of JIBEs imparts unique properties, such as direct 3D-printabilty into aqueous solutions or onto air-exposed surfaces. Their membrane-bound structure also allows functionalization with biological and artificial nanochannels, enabling the material to exhibit the specific properties of the incorporated channels. In this work, we demonstrate three key features of JIBEs using distinct ion channels: tunable conductance, selective transport, and memristance. Incorporating an E. coli outer membrane protein increased ionic conductance by approximately 4,400-fold compared to non-functionalized tissues. Introducing a peptide-based transporter produced ion-selective membranes capable of discriminating ammonium over sodium at a ratio greater than 15:1. Finally, incorporating a model voltage-gated pore enabled the construction of a massively networked memristive device. We propose that functionalizing JIBEs with additional membrane proteins or synthetic ion channels could unlock a broad range of applications, including separations, energy generation and storage, neuromorphic computing, tissue engineering, drug delivery, and soft robotics.

The droplet interface bilayer (DIB) offers a tunable and stable model membrane platform for studying transmembrane proteins (TMPs). Yet, the library of TMPs known to incorporate into DIBs remains limited to those that spontaneously self-insert from aqueous microdroplets. Moreover, incorporating TMP-decorated liposomes into DIB droplets prior to bilayer formation can disrupt lipid assembly and leave TMPs poorly protected from the oil-water interface. We overcome these hurdles by leveraging calcium-mediated vesicle fusion (CMVF) to deliver bilayer-stable TMPs into DIBs via post-bilayer formation microinjection. Departing from prior works, we employed capacitance-based measurements of intrinsic membrane potential to quantify fusion-induced changes in DIB lipid composition. Our results show that CMVF of symmetric, fusogenic liposomes with an asymmetric DIB reduces its transmembrane potential by an amount that corresponds to the fused area of the bilayer: injecting ~40 nL of fusogenic liposomes into one 400 nL droplet resulted in ~15% of the bilayer area becoming less asymmetric in leaflet composition. Moreover, repeated injections produced cumulative vesicle fusion, while omission of fusogenic lipids or Ca2+ ions abolished changes in membrane potential. After quantifying the CMVF process, we used it to enable and enhance the incorporation of multiple TMPs into DIBs. First, injection of proteoliposomes containing TREK-1 proteins, which do not readily insert into DIBs without fusion, consistently produced stochastic, multi-channel gating within minutes. TREK-1 channels exhibited bipolar voltage dependence and pharmacological activation by arachidonic acid, confirming native channel function. Separately, injection of proteoliposomes decorated with OmpF proteins yielded comparable increases in nominal membrane conductance to spontaneously-inserted OmpF proteins, but at half the driving voltage and despite delivering 10X less protein, indicating that fusion incorporates functional TMPs more efficiently than diffusion-limited protein insertion. Together, these results establish capacitance-based measurements and CMVF as a quantitatively verifiable route for improving TMP incorporation into planar lipid bilayers.