Abstract Photothermal therapy (PTT) has garnered significant attention in recent years, but the standalone application of PTT still faces limitations that hinder its ability to achieve optimal therapeutic outcomes. Nitric oxide (NO), being one of the most extensively studied gaseous molecules, presents itself as a promising complementary candidate for PTT. In response, various nanosystems have been developed to enable the simultaneous utilization of PTT and NO‐mediated gas therapy (GT), with the integration of photothermal agents (PTAs) and thermally‐sensitive NO donors being the prevailing approach. This combination seeks to leverage the synergistic effects of PTT and GT while mitigating the potential risks associated with gas toxicity through the use of a single laser irradiation. Furthermore, additional internal or external stimuli have been employed to trigger NO release when combined with different types of PTAs, thereby further enhancing therapeutic efficacy. This comprehensive review aims to summarize recent advancements in NO gas‐assisted cancer photothermal treatment. It commences by providing an overview of various types of NO donors and precursors, including those sensitive to photothermal, light, ultrasound, reactive oxygen species, and glutathione. These NO donors and precursors are discussed in the context of dual‐modal PTT/GT. Subsequently, the incorporation of other treatment modalities such as chemotherapy (CHT), photodynamic therapy (PDT), alkyl radical therapy, radiation therapy, and immunotherapy (IT) in the creation of triple‐modal therapeutic nanoplatforms is presented. The review further explores tetra‐modal therapies, such as PTT/GT/CHT/PDT, PTT/GT/CHT/chemodynamic therapy (CDT), PTT/GT/PDT/IT, PTT/GT/starvation therapy (ST)/IT, PTT/GT/Ca 2+ overload/IT, PTT/GT/ferroptosis (FT)/IT, and PTT/GT/CDT/IT. Finally, potential challenges and future perspectives concerning these novel paradigms are discussed. This comprehensive review is anticipated to serve as a valuable resource for future studies focused on the development of innovative photothermal/NO‐based cancer nanotheranostics. 

Emerging nitric oxide gas‐assisted cancer photothermal treatment

Microneedles are gaining popularity as a new paradigm in the area of transdermal drug delivery for biomedical and healthcare applications. Efficient drug delivery with minimal invasion is the prime advantage of microneedles. The concept of the microneedle array provides an extensive surface area for efficient drug delivery. Various types of inorganics (silicon, ceramic, metal, etc.) and polymeric materials are used for the fabrication of microneedles. The polymeric microneedles have various advantages over other microneedles fabricated using inorganic material, such as biocompatibility, biodegradation, and non-toxicity. The wide variety of polymers used in microneedle fabrication can provide a broad scope for drug delivery and other biomedical applications. Multiple metallic and polymeric microneedles can be functionalized by polymer coatings for various biomedical applications. The fabrication of polymeric microneedles is shifting from conventional to advanced 3D and 4D printing technology. The multifaceted biomedical applications of polymeric microneedles include drug delivery, vaccine delivery, biosensing, and diagnostic applications. Here, we provide the overview of the current and advanced information on polymers used for fabrication, the selection criteria for polymers, biomedical applications, and the regulatory perspective of polymer-based and polymer-coated microneedles, along with a patent scenario.

/pdf/polymeric-microneedles-an-emerging-paradigm-for-advanced-msemrief.pdf

Polymeric Microneedles: An Emerging Paradigm for Advanced Biomedical Applications

Microneedle patches are emerging multifunctional platforms for transdermal diagnostics and drug delivery. However, it still remains challenging to develop smart microneedles integrated with customization, sensing, detection and drug delivery by 3D printing strategy. Here, we present an innovative but facile strategy to rationally design and fabricate multifunctional eutectogel microneedle (EMN) patches via multi-material 3D printing. Polymerizable deep eutectic solvents (PDES) were selected as printing inks for rapid one-step fabrication of 3D printing functional EMN patches due to fast photopolymerization rate and ultrahigh drug solubility. Moreover, stretchable EMN patches incorporating rigid needles and flexible backing layers were easily realized by changing PDES compositions of multi-material 3D printing. Meanwhile, we developed multifunctional smart multi-material EMN patches capable of performing wireless monitoring of body movements, painless colorimetric glucose detection, and controlled transdermal drug delivery. Thus, such multi-material EMN system could provide an effective platform for the painless diagnosis, detection, and therapy of a variety of diseases. 

Multi-material 3D printed eutectogel microneedle patches integrated with fast customization and tunable drug delivery.

Microfluidic chips play crucial roles while lack satisfactory controllability and comprehensive functionality. Inspired by biological systems, this study proposes a method utilizing rolling microneedles (RMNs) to generate muti‐structured templates, realizing photonic crystal membrane (PC) based meta microfluidic microneedle chip (MMM) for efficient wound management. This approach offers advantages in terms of speed and cost‐effectiveness, achieving dual‐sided permeation and patterned design by directly RMNs at desired locations, serving as both template tools for microneedle fabrication. The integration of RMNs with a PC membrane results in the design of 3D multilayer microfluidic channels, effectively addressing issues related to spontaneous fluid flow. As fluid reaches the PC membrane, it generates distinctive structural colors and exhibits fluorescence enhancement, enabling the monitoring of inflammatory factors in mouse wounds and facilitating efficient wound management. In summary, this preparation method involving RMNs paves the way for the design and fluid control of microfluidic chips. This bioinspired patch holds significant potential not only for wound management but also for areas such as clinical drug delivery and point‐of‐care testing (POCT).

Rolling Stone Gathers Moss: Rolling Microneedles Generate Meta Microfluidic Microneedles (MMM)

Microneedle (MN) technology has emerged as a promising approach for delivering therapeutic agents to the skin, offering significant potential in treating various dermal conditions. Among these technologies, hydrogel-forming microneedles (HFMNs) represent a transformative advancement in the management of dermal diseases through non-invasive drug delivery. These innovative devices consist of micrometer-sized needles made of native or crosslinked hydrophilic polymers, capable of penetrating the stratum corneum without damaging underlying tissues. Upon insertion, HFMNs rapidly absorb interstitial fluid, swelling to form a hydrogel conduit that enables the efficient transport of therapeutic agents directly into the dermal microcirculation. The non-invasive nature of HFMNs enhances patient compliance by eliminating the pain and discomfort associated with traditional hypodermic needles. This technology allows for the delivery of a wide range of drugs, including macromolecules and biomacromolecules, which are often difficult to administer dermally due to their size and polarity. Moreover, HFMNs provide controlled and regulated release profiles, enabling sustained therapeutic effects while minimizing systemic side effects. Additionally, HFMNs can be used for both drug delivery and real-time interstitial fluid monitoring, offering valuable insights into disease states and treatment responses. This dual functionality positions HFMNs as a versatile dermatology tool capable of effectively addressing various dermal complications. This review explores the potential use of polymeric biomaterials in HFMN fabrication and their application in treating major dermal disorders, such as acne, psoriasis, and other skin conditions. Furthermore, the review highlights the non-invasive nature of MN-based treatments, underscoring their potential to reduce patient discomfort and improve treatment adherence, as supported by the recent literature. 

Hydrogel-Forming Microneedles in the Management of Dermal Disorders Through a Non-Invasive Process: A Review

The remarkable appeal of microneedle controlled-release systems has captivated both the academic community and pharmaceutical industry due to their great potential for achieving spatiotemporally controlled release, coupled with the minimally invasive nature and ease of application. Over the years, scientists have dedicated their efforts to advancing microneedle systems by manipulating the physicochemical properties of matrix materials, refining microneedle designs, and interfacing with external devices to provide tailored drug release profiles in a spatiotemporally controllable manner. Expanding upon our understanding of drug release mechanisms from polymeric microneedles, which include diffusion, swelling, degradation, triggering, and targeting, there is a growing focus on manipulating the location and rate of drug release through innovative microneedle designs. This burgeoning field of microneedle-based drug delivery systems offers further prospects for precise control over drug release. The design strategies of polymeric microneedle systems for temporally controlled and locally targeted release, as well as the delivery mechanisms by which drugs can be released from a microneedle system are critically reviewed in this work. Furthermore, this review also puts forward some perspectives on the potential and challenges involved in translating these microneedle-based delivery systems into the next generation therapies. 

Strategies to develop polymeric microneedles for controlled drug release

Hydroquinone cream-based polymer microneedle roller for the combined treatment of large-area chloasma

Monitoring the change of the giant panda habitat is essential to protect this endangered species. The Wolong National Nature Reserve (WNNR) of China, the giant panda habitat, was struck by the Wenchuan earthquake (M=8.0) on May 12, 2008, and was seriously damaged. Landsat images covering the WNNR on four dates, one before and three after the earthquake, are classified using support vector machines to generate land cover maps (with an overall accuracy of ∼90% and Kappa coefficients of ∼0.86). The habitat suitability index and weighted usable area (WUA) are calculated to evaluate the changes of the habitat suitability of the WNNR. The results indicate that the forest area dropped by ∼10% due to the earthquake. The forest located in the east of Wolong town, the home of numerous giant pandas, suffered the most. The WUA decreased significantly after the earthquake, and was showing improvement in 2013, although still not fully recovered to the level of priori earthquake. The habitat between 1200 and 1300 m above sea level (m a.s.l.) was particularly vulnerable and was slowly recovering. Further effective management is necessary to restore and protect the giant panda habitat.

Impact of Wenchuan earthquake on the giant panda habitat in Wolong National Nature Reserve, China

An aptamer-integrated conductive microneedle biosensor for real-time transdermal cortisol monitoring

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Strategies to develop polymeric microneedles for controlled drug release

Hydroquinone cream-based polymer microneedle roller for the combined treatment of large-area chloasma

Impact of Wenchuan earthquake on the giant panda habitat in Wolong National Nature Reserve, China

An aptamer-integrated conductive microneedle biosensor for real-time transdermal cortisol monitoring