Cancer treatment has undergone a paradigm shift following the introduction of novel cancer treatment approaches that involve the host’s immune system in fighting established tumors. This new concept aids the immune system in identifying, attacking, and killing the tumor cells. However, although some encouraging results were observed clinically, this approach has its own limitations. For example, the benefits of certain anticancer drugs were only observed in some patients, off-target effects, immune evasion, and poor pharmacokinetics. Recently, several advancements have been made with the understanding and development of tumor-targeted drug delivery systems, which combine both effectiveness and patients’ safety during cancer treatment. In this review, we will focus on the latest progress in targeted drug delivery, particularly applying nanoparticles, liposomes, exosomes, and Wharton’s jelly-derived macrovesicles as immune cell enhancers, as well as overcoming therapeutic resistance. We also characterize major current problems, such as the biocompatibility and scalability of the delivered engineering systems, as well as the required regulations. Lastly, we will show some examples of effective approaches to resolve these issues for more efficient cancer therapy. The importance of this article lies in bridging two sides in a single framework perspective: the novel implementation of unique delivery systems and the latest advances in the field of cancer immunotherapy. Thus, this provides better insights for the future of cancer treatment.

Conventional immunotherapy, including immune checkpoint blockade and chimeric antigen receptor (CAR)-T cells, has revolutionized cancer therapy over the past decade. Yet, the efficacy of these therapies is limited by tumor resistance, antigen escape mechanisms, poor persistence, and T-cell exhaustion, particularly in the treatment of solid tumors. The emergence of unconventional immunotherapies offers novel opportunities by leveraging diverse immune cell subsets and synthetic biologics. This review explores various immunotherapy platforms, including gamma delta T cells, invariant natural killer T cells, mucosal-associated invariant T cells, engineered regulatory T cells, and universal CAR platforms. Additionally, it expands on biologics, including bispecific and multispecific antibodies, cytokine fusions, agonists, and oncolytic viruses, showcasing their potential for modular engineering and off-the-shelf applicability. Distinct features of unconventional platforms include independence from the major histocompatibility complex (MHC), tissue-homing capabilities, stress ligand sensing, and the ability to bridge adaptive and innate immunity. Their compatibility with engineering approaches highlights their potential as scalable, efficient, and cost-effective therapies. To overcome translational challenges such as functional heterogeneity, immune exhaustion, tumor microenvironment-mediated suppression, and limited persistence, novel strategies will be discussed, including metabolic and epigenetic reprogramming, immune cloaking, gene editing, and the utilization of artificial intelligence for patient stratification. Ultimately, unconventional immunotherapies extend the therapeutic horizon of cancer immunotherapy by breaking barriers in solid tumor treatment and increasing accessibility. Continued investments in research for mechanistic insights and scalable manufacturing are key to unlocking their full clinical potential.

Background: Non-communicable diseases (NCDs) such as cardiovascular diseases, diabetes, obesity, and cancer are the leading cause of mortality globally and in Saudi Arabia, accounting for more than 70% of all deaths. Despite national initiatives offering free preventive services, screening uptake remains low. This study aimed to describe the demographic and clinical characteristics of individuals participating in community-based NCD screening campaigns in the Eastern Province of Saudi Arabia and to evaluate screening uptake, compliance, and diagnostic outcomes. Methods: A retrospective cross-sectional analysis was conducted among 3106 adults screened at volunteer-driven community campaigns held between January 2023 and December 2024. Screening included anthropometric measurements, blood pressure assessment, and glucose testing, followed by eligibility evaluation for osteoporosis and cancer screening. Uptake and compliance were verified using electronic health records. Descriptive and inferential statistical analyses were applied. Results: Participants were 64% male and 36% female, with a mean age of 41.4 ± SD years. Obesity, hypertension, and diabetes were identified in 32%, 31%, and 12% of participants overall. Gender-stratified prevalence showed higher obesity among females at 36% (95% CI 32.3 to 38.1) and higher hypertension and diabetes among males at 36% (95% CI 34.0 to 38.2) and 14% (95% CI 12.1 to 15.2), respectively. Uptake among eligible individuals was 51% for dual-energy X-ray absorptiometry (DEXA), 47% for fecal immunochemical testing (FIT), 43% for Pap smear, and 39% for mammography. Diagnostic findings demonstrated substantial undetected disease burden, including osteoporosis in 41% (95% CI 26.0 to 56.8) of DEXA scans, a FIT positivity rate of 5% (95% CI 1.5 to 10.3), abnormal Pap cytology in 3% (95% CI 1.1 to 7.5), and BI-RADS 0 mammograms in 19% (95% CI 11.9 to 29.5), reflecting incomplete assessments requiring further evaluation. Conclusions: Community-based campaigns can effectively resolve limited engagement in health promotional activities and detect substantial burdens of undiagnosed NCDs. However, improvements in referral tracking, follow-up systems, and culturally tailored health education are essential to enhance screening compliance and early detection outcomes. These results can be utilized to inform public policies by extending screening services to additional areas, increasing investment in preventive health campaigns, and enhancing the capacity of the health system.

RNA vaccines have emerged as an attractive platform for treating infectious diseases, cancer immunotherapy, and personalized medicine; however, their clinical success depends on multiple factors, including efficient, stable, and scalable delivery systems. Because RNA molecules are highly sensitive to factors such as enzymatic degradation, oxidation, poor cellular uptake, and limited endosomal escape, nanocarrier platforms play essential roles in protecting RNA cargo and enabling effective intracellular delivery. The biological performance of RNA nanocarriers depends on efficient cellular uptake, endosomal escape, intracellular RNA delivery, biodistribution, and immune modulation. Comparative assessment emphasizes that lipid nanoparticles remain the most clinically mature approach, while nanostructured lipid carriers, polymeric systems, and exosome-based nanocarriers provide multiple benefits for stability, targeted delivery, biocompatibility, and/or controlled release. Translational challenges involving GMP manufacturing, batch reproducibility, regulatory expectations, and scale-up are considered critical for effective nano-based RNA vaccine delivery and are elaborated in this review. Emerging advances such as pKa-tuned ionizable lipids, ligand-targeted systems, stimuli-responsive nanocarriers, circular and self-amplifying RNA platforms, artificial intelligence-guided formulation design, and needle-free delivery technologies may further expand the safety, accessibility, and therapeutic potential of RNA vaccines. In this review, we highlight next-generation nanocarrier systems for RNA vaccines, with an emphasis on novel nanocarrier RNA vaccine delivery systems. Additionally, we evaluate stability engineering approaches that currently limit global vaccine distribution and the future of the nanocarrier platforms for RNA vaccines.

Plant-derived natural products are essential and prominent contributors to drug discovery, especially as anticancer agents. Medicinal plants used in alternative therapy are often obscured by poor definitions of the underlying mechanisms behind their bioactivity. In this study, we investigated the cytotoxic and mechanistic effects of an enriched bioactive fraction derived from Mondia whitei. Bioactivity-guided fractionation was performed using C18 solid-phase extraction. The cytotoxic effects were evaluated using the MTT assay, while cellular morphology and mechanistic pathways were examined through microscopy, acridine orange staining, cathepsin-based assay, and immunoblotting of apoptosis- and autophagy-related proteins. Chemical profiling of the fraction was conducted using GC–MS analysis. The enriched fraction exhibited enhanced cytotoxicity at low microgram concentrations. Morphological assessment revealed prominent cytoplasmic vacuolation, while acridine orange staining indicated the accumulation of acidic vesicles. Cathepsin-based assays and immunoblot analysis of LC3-I/II confirmed lysosomal involvement and autophagy perturbation, whereas increased p62 levels suggested disruption of the autophagy–lysosome perturbation. In parallel, activation of intrinsic apoptosis was evidenced by the increased expression of caspase-9 and caspase-3. GC–MS profiling tentatively identified lupeol and cis-vaccenic acid as the major constituents of the fraction. The results from these studies demonstrate that the enriched fraction of Mondia whitei induced vacuolation-associated cytotoxicity through autophagy–lysosome perturbation and caspase-dependent apoptosis, providing mechanistic insight into its anticancer potential.

Ribonucleic acid-based vaccines have emerged as one of the most significant advances in modern vaccine development, demonstrating remarkable clinical success and enabling rapid responses to emerging infectious diseases. Despite their therapeutic potential, the development of these vaccines remains challenging because of the inherent instability of ribonucleic acid molecules, their susceptibility to degradation, and the complexity of formulation design. Ensuring product quality, stability, and biological performance therefore requires comprehensive analytical characterization throughout development, manufacturing, storage, and quality control. This review provides a comprehensive overview of current analytical strategies used to evaluate ribonucleic acid-based vaccine formulations. Key analytical approaches for assessing molecular integrity, purity, encapsulation efficiency, particle morphology, size distribution, surface characteristics, structural attributes, and biological potency are discussed. The review also examines the influence of formulation composition, lipid nanoparticle design, manufacturing processes, and storage conditions on vaccine stability and performance. In addition, major degradation pathways, critical quality attributes, and analytical challenges associated with quality assessment are highlighted. Furthermore, current regulatory considerations and limitations of existing analytical methodologies are discussed, particularly the challenges associated with establishing robust relationships between physicochemical properties and biological efficacy. The review emphasizes the importance of integrated multi-method analytical approaches for comprehensive characterization and quality assurance. Continued advances in analytical technologies and standardization efforts will be essential for supporting the development of safe, effective, and stable ribonucleic acid-based vaccines and for facilitating their broader pharmaceutical applications.