Jeremiah J. Gassensmith

Overexpression of transmembrane Cu(I) P‐type ATPase pumps in cancer cells correlates with drug resistance towards chemotherapeutic Pt(II)‐based drugs, suggesting that they may facilitate the vesicular sequestration and cellular efflux of Pt(II)‐complexes. However, the ability of Cu(I)‐pumps to translocate Pt(II)‐drugs, including the molecular principles behind cargo recognition, remains elusive due to lack of tools to monitor in vitro turnover Pt(II)‐translocation events with transporters reconstituted into membrane‐mimetic systems. Here, we developed supramolecular mercaptosuccinic acid‐capped CdTe core‐type quantum dot‐encapsulated proteoliposome assemblies (MSA‐CdTe QD PLs) to demonstrate real‐time transporter‐mediated turnover translocation of Pt(II)‐complexes by Cu(I) P‐type ATPases. We coupled Pt(II)‐complex‐stimulated ATPase activity assays on the purified E. coli Cu(I)‐pump CopA with reconstitution into proteoliposomes and real‐time transport assays utilizing fluorescence detector probes (MSA‐CdTe QDs, pyranine, and oxonol VI) responsive to substrate, pH, and membrane potential, to demonstrate that Cu(I)‐pumps are electrogenic Pt(II)‐drug uniporters. Cu(I)‐pumps efficiently translocate aquated Pt(II)‐complexes with cis configuration (like cisplatin and carboplatin), but not transplatin, emphasizing how stereochemistry influences the Pt(II) transport properties. Additionally, the nature and kinetic lability of the carrier and leaving ligands were demonstrated to modulate the transport activity. Overall, MSA‐CdTe QD proteoliposome assemblies establish an extendable experimental platform to discover the Pt(II) transport properties of novel transporter classes.

Overexpression of transmembrane Cu(I) P‐type ATPase pumps in cancer cells correlates with drug resistance towards chemotherapeutic Pt(II)‐based drugs, suggesting that they may facilitate the vesicular sequestration and cellular efflux of Pt(II)‐complexes. However, the ability of Cu(I)‐pumps to translocate Pt(II)‐drugs, including the molecular principles behind cargo recognition, remains elusive due to lack of tools to monitor in vitro turnover Pt(II)‐translocation events with transporters reconstituted into membrane‐mimetic systems. Here, we developed supramolecular mercaptosuccinic acid‐capped CdTe core‐type quantum dot‐encapsulated proteoliposome assemblies (MSA‐CdTe QD PLs) to demonstrate real‐time transporter‐mediated turnover translocation of Pt(II)‐complexes by Cu(I) P‐type ATPases. We coupled Pt(II)‐complex‐stimulated ATPase activity assays on the purified E. coli Cu(I)‐pump CopA with reconstitution into proteoliposomes and real‐time transport assays utilizing fluorescence detector probes (MSA‐CdTe QDs, pyranine, and oxonol VI) responsive to substrate, pH, and membrane potential, to demonstrate that Cu(I)‐pumps are electrogenic Pt(II)‐drug uniporters. Cu(I)‐pumps efficiently translocate aquated Pt(II)‐complexes with cis configuration (like cisplatin and carboplatin), but not transplatin, emphasizing how stereochemistry influences the Pt(II) transport properties. Additionally, the nature and kinetic lability of the carrier and leaving ligands were demonstrated to modulate the transport activity. Overall, MSA‐CdTe QD proteoliposome assemblies establish an extendable experimental platform to discover the Pt(II) transport properties of novel transporter classes.

Inspired by the DNA-cleaving potency of natural enediynes such as calicheamicin, we report the design and synthesis of maleimide−enediyne conjugates integrated into poly(ε-caprolactone) (PCL) as a next-generation platform for anticancer drug delivery. Maleimide-based enediynes typically suffer from poor aqueous solubility and nonspecific toxicity, addressed here by covalently incorporating enediyne groups into amphiphilic PCL block copolymers via post-polymerization functionalization. The resulting polymers form ∼120 nm spherical micelles with a critical micelle concentration of 9.1 × 10−4 mg mL−1, enhancing enediyne solubility, promoting tumor accumulation through the EPR effect, and enabling encapsulation of hydrophobic drugs such as doxorubicin. Electron paramagnetic resonance confirmed radical formation and Bergman cyclization under physiological conditions. Cell viability assays showed enediyne-induced death in MDA-MB-231 breast cancer cells, and the functionalized PCL exhibited in vitro DNA cleaving activity, demonstrating that maleimide−enediyne-functionalized PCL micelles are promising platforms for cancer chemotherapy.

Self‐assembling peptide fibers have many applications, including tissue engineering, drug delivery, and environmentally friendly textile materials. However, previous studies used peptides that self‐assemble, limiting their potential for large‐scale synthesis. In the current study, three peptides were designed: a negatively charged 21‐residue peptide (21n), a negatively charged 28‐residue peptide (28n), and a positively charged 35‐residue peptide (35p). Peptides of opposite charges that were exposed to each other co‐assembled into α‐helical coiled‐coils. Peptides of different lengths allow for the formation of sticky ends, encouraging linear growth. The peptides include cysteine residues to stabilize fiber growth. Circular dichroism confirmed stable alpha‐helical secondary structure, and aggregation assays were conducted to track the assembly of higher‐order structures. Transmission electron microscopy was used to visually examine the aggregates that formed. When mixed, the designed peptides co‐assembled into large, fibrous aggregates. These fibers were resistant to heat and salt, but they disassembled when exposed to a reducing agent such as dithiothreitol (DTT). Fibers made by pairing 21n or 28n to 35p resulted in different morphologies upon co‐assembly under oxidizing conditions. Peptides that are soluble independently but co‐assemble into large, disulfide‐reinforced fibers present a new platform for tunable, biologically inspired fibers.

Capturing and stabilizing microbes and viruses from complex samples typically requires filtration/ultracentrifugation, affinity reagents, or cold‐chain transport. Here we show that a single aqueous Zn(II)/2‐methylimidazole formulation maintaining a 1 × 80 metal‐to‐ligand molar ratio (1 mM Zn(OAc)2·2H2O and 80 mM 2‐methylimidazole) rapidly mineralizes a Zn–methylimidazolate coating on diverse biological templates, causing them to coprecipitate for recovery by low‐speed centrifugation. The coating is removed on demand using phosphate‐containing, low pH solutions or growth media enabling revival of E. coli , S. aureus , and C. albicans following up to 14 days of ambient storage. For viruses, encapsulation reduces ambient infectivity losses (e.g., reovirus retains substantially higher titers than uncoated controls after extended storage). To eliminate solution preparation, we further introduce a solid “ZIF pill” (ZIP) that dissolves directly in samples to generate the 1 × 80 ratio in situ, delivering 3 mM Zn(OAc) ₂ ·2H ₂ O and 240 mM 2‐methylimidazole. The ZIP pill enables reproducible, on‐demand encapsulation and recovery. Together, the 1 × 80 liquid formulation and ZIP tablets provide a scalable, field‐deployable workflow for gentle capture and preservation of microbes and viruses for downstream culture and analysis.

Metal–organic frameworks (MOFs) entered biomedicine through a simple idea: their permanent porosity made them attractive materials for cargo loading, protection, and release. This perspective argues that, with few exceptions, biomedical MOFs are not biologically inert carriers and should not be developed as though they were. In biological environments, they behave instead as metastable, structurally dynamic, programmable coordination materials whose composition, particle structure, and environmental transformation directly shape biological outcomes. This case is developed through three interconnected themes: coordinated disassembly and transient protection; nonideal particulate transport shaped by size, morphology, and defects; and framework-derived biological activity arising from metals, ligands, and degradation products. Together, these features show why MOF performance in biology is poorly described by surface area, pore volume, and loading capacity alone. The more productive direction is therefore not to ignore or suppress framework bioactivity, but to work with it deliberately, treating the framework itself as part of the mechanism by which a biomedical MOF functions. Viewed this way, the future of the field lies less in approximating passive delivery systems and more in engineering dynamic materials whose disassembly, trafficking, and compositional bioactivity can be used to shape biological responses.

Organophosphate (OP) poisoning is among the most lethal forms of chemical intoxication, commonly occurring in both warfare and agricultural settings. Although enzyme-based detoxification strategies, such as organophosphorus acid anhydrolase (OPAA), have shown promise in vitro , their rapid clearance and instability have severely limited their clinical translation. Here, we report the first in vivo study demonstrating the use of metal–organic frameworks (MOFs) as delivery depots for sustained OP detoxification. OPAA was successfully encapsulated within two MOFs—zeolitic imidazolate framework-8 (ZIF-8) and NU-1003—using biomimetic mineralization and passive diffusion strategies, respectively. These composites provided prolonged subcutaneous retention, preserved enzymatic activity, and offered complete protection in mice exposed to lethal doses of OP agents. In addition to immediate post-exposure rescue, the system also functioned as a long-acting prophylactic with minimal immunogenicity and excellent biocompatibility. This dual-use approach provides a powerful new platform for enzyme therapeutics, where both sustained activity and rapid response are required.

We report the discovery and synthesis of MOXI-214, a manganese-based metal–organic framework (MOF) with high selectivity for CO ₂ adsorption.

L-T6 FRET Probe (50 nM) stability in vitro (10% FBS, PBS). Excitation = 475 nm.

This work presents a strategy to target bacteria-infected living cells selectively. A charged zinc complex conjugated to a near-infrared reporter permeates cell membranes and binds bacterial selectively in vitro and in vivo.