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The effective and efficient treatment of diseases, such as HIV, cancer or hereditary diseases, requires accurate and precise control of the combinatorial drug-dosage and their release. Herein, we introduce a simple photosensitive poly(ethylene glycol) diacrylate (PEGDA) hydrogel based platform for high dynamic range testing of combinatorial cocktail drug screening using three chemical and two protein drug treatments for colon cancer. UV cross linked PEGDA hydrogel droplet arrays on a Teflon patterned glass substrate enable a rapid yet accurate selection and dosage assignment of the drugs. Precisely loaded cocktails of the anticancer drugs were simultaneously released in-parallel with the PEGDA hydrogel chips into 2D or 3D cultured HCT-8 colon cancer cells for combinatorial drug screening. We demonstrate the functionality of our UV gel-Drug Chips 1000 fold range of concentrations for each of the five drugs in 30 seconds to find the optimized drug cocktail using a fractional factorial control system. Our device has low drug consumption, requiring only 12 nL per screening run per droplet. In addition, our UV gel-Drug Chips were employed for find the optimized drug cocktail using a fractional search algorithm. Our cocktail drug response results for both 2D (cell viability is 7.3%) and 3D (cell viability is 10.8%) colon cancer cells were analogous to those found by conventional method (6.8 and 9.3 respectively). In contrast to conventional method, our approach is faster, more effective, less time consuming and requires a lower amounts of drug volume.

Unraveling the intricacies between oxygen dynamics and cellular processes in the tumor microenvironment (TME) hinges upon precise monitoring of intracellular and intratumoral oxygen levels, which holds paramount significance. The majority of these reported oxygen nanoprobes suffer compromised lifetime and quantum yield when exposed to the robust ROS activities prevalent in TME, limiting their prolonged in vitro usability. Herein, the ruthenium-embedded oxygen nano polymeric sensor (Ru-ONPS) is proposed for precise oxygen gradient monitoring within the cellular environment and TME. Ru-ONPS (≈64±7 nm) incorporates [Ru(dpp) 3 ]Cl 2 dye into F-127 and crosslinks it with urea and paraformaldehyde, ensuring a prolonged lifetime (5.4 µs), high quantum yield (66.65 ± 2.43% in N 2 and 49.80 ± 3.14% in O 2 ), superior photostability (>30 min), and excellent stability in diverse environmental conditions. Based on the Stern-Volmer plot, the Ru-ONPS shows complete linearity for a wide dynamic range (0-23 mg L -1 ), with a detection limit of 10 µg mL -1 . Confocal imaging reveals Ru-ONPS cellular uptake and intratumoral distribution. After 72 h, HCT-8 cells show 5.20±1.03% oxygen levels, while NIH3T3 cells have 7.07±1.90%. Co-culture spheroids display declining oxygen levels of 17.90±0.88%, 10.90±0.88%, and 5.10±1.18%, at 48, 120, and 216 h, respectively. Ru-ONPS advances cellular oxygen measurement and facilitates hypoxia-dependent metastatic research and therapeutic target identification., (© 2023 Wiley‐VCH GmbH.)

Copper sulfide nanoparticles (CuS NPs) have attracted growing interest in biomedical research due to their remarkable properties, such as their high photothermal and thermodynamic capabilities, which are ideal for anticancer and antibacterial applications. This comprehensive review focuses on the current state of antitumor and antibacterial applications of CuS NPs. The initial section provides an overview of the various approaches to synthesizing CuS NPs, highlighting the size, shape and composition of CuS NPs fabricated using different methods. In this review, the mechanisms underlying the antitumor and antibacterial activities of CuS NPs in medical applications are discussed and the clinical challenges associated with the use of CuS NPs are also addressed.

Rapid and sensitive diagnostics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of utmost importance to control the widespread coronavirus disease 2019 (COVID-19) upsurge. This study demonstrated a novel one-pot surface-enhanced Raman scattering (SERS) based immunoassay to detect SARS-CoV-2, without any washing process using a portable Raman spectrometer. The SERS-immune assay was designed using a regular digital versatile disk (DVD) substrate integrated with Raman reporter labeled silver nanoparticles for double clamping effects. The disks were molded to form nanopillar arrays and coated with silver film to enhance the sensitivity of immunoassay. The SERS platform demonstrated a limit of detection (LoD) up to 50 pg mL -1 for SARS-CoV-2 spike protein and virus-like-particle (VLP) protein in phosphate buffer saline within a turnaround time of 20 mins. Moreover, VLP protein spiked in untreated saliva achieved an LoD of 400 pg mL -1 , providing a cycle threshold (Ct) value range of 30-32, closer to reverse transcription-polymerase chain reaction (RT-PCR) results (35-40) and higher than the commercial rapid antigen tests, ranging from 25 to 28. Therefore, the developed one-pot SERS based biosensor exhibited highly sensitive and rapid detection of SARS-CoV-2, which could be a potential point-of-care platform for early and cost-effective diagnosis of the COVID-19 virus., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Elsevier B.V. All rights reserved.)

Temperature governs the reactivity of a wide range of biomolecules in the cellular environment dynamically. The complex cellular pathways and molecules in solid tumors substantially produce temperature gradients in the tumor microenvironment (TME). Hence, visualization of these temperature gradients at the cellular level would give physiologically relevant spatio-temporal information about solid tumors. This study used fluorescent polymeric nano-thermometers (FPNTs) to measure the intratumor temperature in co-cultured 3D tumor spheroids. A temperature-sensitive rhodamine-B dye and Pluronic F-127 were conjugated through hydrophobic and hydrophobic interactions and then cross-linked with urea-paraformaldehyde resins to form the FPNTs. The characterization results exhibit monodisperse nanoparticles (166 ± 10 nm) with persistent fluorescence. The FPNTs exhibit a linear response with a wide temperature sensing range (25-100 °C) and are stable toward pH, ionic strength, and oxidative stress. FPNTs were utilized to monitor the temperature gradient in co-cultured 3D tumor spheroids and the temperature difference between the core (34.9 °C) and the periphery (37.8 °C) was 2.9 °C. This investigation demonstrates that the FPNTs have great stability, biocompatibility, and high intensity in a biological medium. The usage of FPNTs as a multifunctional adjuvant may demonstrate the dynamics of the TME and they may be suitable candidates to examine thermoregulation in tumor spheroids.

Background: Boron neutron capture therapy (BNCT) is a promising cancer treatment that eliminates tumor cells by triggering high-energy radiation within cancer cells. Aim: In vivo evaluation of poly(vinyl alcohol)/boric acid crosslinked nanoparticles (PVA/BA NPs) for BNCT. Materials & methods: PVA/BA NPs were synthesized and intravenously injected into tumor-bearing mice for BNCT. Results: The in vitro boron uptake of PVA/BA NPs in tumor cells was 70-fold higher than the required boron uptake for successful BNCT. In an in vivo study, PVA/BA NPs showed a 44.29% reduction in tumor size compared with clinically used boronophenylalanine for oral cancer in a murine model. Conclusion: PVA/BA NPs exhibited effective therapeutic results for oral cancer treatments in BNCT.

Three-dimensional (3D) spheroid culture provides opportunities to model tumor growth closer to its natural context. The collagen network in the extracellular matrix supports autonomic tumor cell proliferation, but its presence and role in tumor spheroids remain unclear. In this research, we developed an in vitro 3D co-culture model in a microwell 3D (μ-well 3D) cell-culture array platform to mimic the tumor microenvironment (TME). The modular setup is used to characterize the paracrine signaling molecules and the role of the intraspheroidal collagen network in cancer drug resistance. The μ-well 3D platform is made up of poly(dimethylsiloxane) that contains 630 round wells for individual spheroid growth. Inside each well, the growth surface measured 500 μm in diameter and was functionalized with the amphiphilic copolymer. HCT-8 colon cancer cells and/or NIH3T3 fibroblasts were seeded in each well and incubated for up to 9 days for TME studies. It was observed that NIH3T3 cells promoted the kinetics of tumor organoid formation. The two types of cells self-organized into core-shell chimeric tumor spheroids (CTSs) with fibroblasts confined to the shell and cancer cells localized to the core. Confocal microscopy analysis indicated that a type-I collagen network developed inside the CTS along with increased TGF-β1 and α-SMA proteins. The results were correlated with a significantly increased stiffness in 3D co-cultured CTS up to 52 kPa as compared to two-dimensional (2D) co-culture. CTS was more resistant to 5-FU (IC 50 = 14.0 ± 3.9 μM) and Regorafenib (IC 50 = 49.8 ± 9.9 μM) compared to cells grown under the 2D condition 5-FU (IC 50 = 12.2 ± 3.7 μM) and Regorafenib (IC 50 = 5.9 ± 1.9 μM). Targeted collagen homeostasis with Sclerotiorin led to damaged collagen structure and disrupted the type-I collagen network within CTS. Such a treatment significantly sensitized collagen-supported CTS to 5-FU (IC 50 = 4.4 ± 1.3 μM) and to Regorafenib (IC 50 = 0.5 ± 0.2 μM). In summary, the efficient formation of colon cancer CTSs in a μ-well 3D culture platform allows exploration of the desmoplastic TME. The novel role of intratumor collagen quality as a drug sensitization target warrants further investigation.