Photoaging, the premature aging of skin due to chronic ultraviolet (UV) exposure, is a growing concern in dermatology and cosmetic science. While UV radiation is known to induce DNA damage, oxidative stress, and inflammation in skin cells, recent research unveils a promising countermeasure: autophagy. This review explores the intricate relationship between autophagy and photoaging, highlighting how this cellular recycling process can mitigate UV-induced damage. We begin by examining the differential impacts of UVA and UVB radiation on skin cells and the role of oxidative stress in accelerating photoaging. Next, we delve into the molecular mechanisms of autophagy, including its various forms and regulatory pathways. Central to this review is the discussion of autophagy’s protective functions, such as the clearance of damaged organelles and proteins, and its role in maintaining genomic integrity. Furthermore, we address the current challenges in harnessing autophagy for therapeutic purposes, including the need for selective autophagy inducers and a deeper understanding of its context-dependent effects. By synthesizing recent advancements and proposing future research directions, this review underscores the potential of autophagy modulation as a novel strategy to prevent and treat photoaging. This comprehensive analysis aims to inspire further investigation into autophagy-based interventions, offering new hope for preserving skin health in the face of environmental stressors.

Despite significant advancements in nanomaterials for cancer therapy, the clinical translation of cancer nanomedicine remains greatly hindered by insufficient accumulation of these nanomaterials within solid tumors—a critical bottleneck underlying the high failure rates observed in clinical trials. Our review systematically analyzes the mechanisms governing nanomaterial delivery to solid tumors, extending beyond the foundational Enhanced Permeability and Retention (EPR) effect. We critically evaluate passive strategies leveraging physicochemical properties (size switching, charge reversal) and tumor microenvironment (TME) modulation to amplify EPR-dependent delivery. Furthermore, we dissect active targeting paradigms—including ligand-directed, aptamer-based, and cell-mediated strategies, which exploit the distinct molecular and cellular characteristics of solid tumors to improve nanomaterial specificity and cellular uptake. Crucially, we highlight the bidirectional relationship between nanomedicine accumulation and TME dynamics, alongside the associated cytotoxic consequences. The review emphasizes the paradigm shift toward "passive–active" dual-targeting strategies and emerging technologies designed to overcome sequential physiological barriers. By integrating fundamental transport mechanisms, therapeutic efficacy, and toxicity profiles, this review offers a comprehensive framework for the rational design of next-generation nanomaterials with enhanced solid tumor accumulation and clinical applicability.

Cancer-associated fibroblasts (CAFs) play a crucial role in the tumor microenvironment by promoting tumor growth, immune evasion, and metastasis. Recently, drug delivery systems targeting CAFs have emerged as a promising long-term and effective approach to cancer treatment. Advances in nanotechnology, in particular, have led to the development of nanomedicine delivery systems designed specifically to target CAFs, offering new possibilities for precise and personalized cancer therapies. This article reviews recent progress in drug delivery using nanocarriers that target CAFs. Additionally, we explore the potential of combining multiple therapies, such as chemotherapy and immunotherapy, with nanocarriers to enhance efficacy and overcome drug resistance. Although many preclinical studies show promise, the clinical application of nanomedicine still faces considerable challenges, especially in terms of drug penetration and large-scale production. Therefore, this review aims to provide a fresh perspective on CAF-targeted drug delivery systems and highlight potential future research directions and clinical applications.

Cancer-associated fibroblasts (CAFs) are a heterogeneous population of non-malignant cells that play a crucial role in the tumor microenvironment, increasingly recognized as key contributors to cancer progression, metastasis, and treatment resistance. So, targeting CAFs has always been considered an important part of cancer immunotherapy. However, targeting CAFs to improve the efficacy of tumor therapy is currently a major challenge. Nanomaterials show their unique advantages in the whole process. At present, nanomaterials have achieved significant accomplishments in medical applications, particularly in the field of cancer-targeted therapy, showing enormous potential. It has been confirmed that nanomaterials can not only directly target CAFs, but also interact with the tumor microenvironment (TME) and immune cells to affect tumorigenesis. As for the cancer treatment, nanomaterials could enhance the therapeutic effect in many ways. Therefore, in this review, we first summarized the current understanding of the complex interactions between CAFs and TME, immune cells, and tumor cells. Next, we discussed common nanomaterials in modern medicine and their respective impacts on the TME, CAFs, and interactions with tumors. Finally, we focus on the application of nano drug delivery system targeting CAFs in cancer therapy.

Emphasizing the significance of cancer-associated fibroblasts (CAFs), non-malignant yet pivotal players within the tumor microenvironment (TME), this review illuminates the role of inflammatory subtype (iCAF) as catalysts in cancer proliferation, metastasis, and therapeutic resistance. Given their paramount importance, targeting CAFs emerges as a robust strategy in the evolving landscape of cancer immunotherapy. Nanomaterials, distinguished by their unique features and malleability, hold considerable promise in biomedicine, especially in the precision-oriented domain of cancer therapy. Their aptitude for modulating immune responses, amplifying drug efficacy through precise delivery, and discerningly focusing on cells within the TME situates nanomaterials as formidable tools to transcend the boundaries set by conventional treatments. This review scrutinizes the convoluted interplay among CAFs, immune cells, and tumor cells within the TME. It further showcases widely utilized nanomaterials in cancer management. We underscore the potential of nanoscale drug delivery systems directed at CAFs, underscoring their transformative power in revolutionizing cancer therapies, enhancing precision, and culminating in improved patient outcomes.

The clinical advancement of cancer nanomedicine is significantly hindered by its limited accumulation in tumors, a key factor behind the frequent failure of nanodrugs in clinical trials. The effectiveness of these nanodrugs is closely tied to their route of administration, whether oral, transdermal, intravenous, or intracerebral, as each path presents unique physiological barriers that impede bioavailability and precise tumor targeting. Among the major causes of poor accumulation are rapid clearance by the mononuclear phagocyte system, opsonization accompanied by protein corona formation, renal filtration, and the abnormal, heterogeneous nature of tumor vasculature that restricts passive targeting via the enhanced permeability and retention (EPR) effect. In response, active targeting (AT) strategies have been widely explored, including surface modification with ligands, antibodies, or aptamers designed to bind specifically to overexpressed receptors on cancer cells or blood vessels. Despite these efforts, challenges such as the dense extracellular matrix, elevated interstitial fluid pressure, and the notable inconsistency of the EPR effect between animal models and human patients continue to limit therapeutic penetration. This review offers a systematic examination of nanodrug delivery pathways and the reasons behind their inadequate accumulation, highlighting the potential of both active targeting and combined passive-active strategies to enhance tumor-specific delivery. Overcoming these biological barriers through refined nano-design is crucial for developing the next generation of nanomedicines with improved tumor accumulation and treatment outcomes.