Targeted drug delivery is a precise and effective strategy in oncotherapy that can accurately deliver drugs to tumor cells or tissues to enhance their therapeutic effect and, meanwhile, weaken their undesirable side effects on normal cells or tissues. In this research field, a large number of researchers have achieved significant breakthroughs and advances in oncotherapy. Typically, nanocarriers as a promising drug delivery strategy can effectively deliver drugs to the tumor site through enhanced permeability and retention (EPR) effect-mediated passive targeting and various types of receptor-mediated active targeting, respectively. Herein, we review recent targeted drug delivery strategies and technologies for enhancing oncotherapy. In addition, we also review two mainstream drug delivery strategies, passive and active targeting, based on various nanocarriers for enhancing tumor therapy. Meanwhile, a comparison and combination of passive and active targeting are also carried out. Furthermore, we discuss the associated challenges of passive and active targeted drug delivery strategies and the prospects for further study.

Photothermal therapy (PTT) is a promising cancer therapy modality with significant advantages such as precise targeting, convenient drug delivery, better efficacy, and minimal adverse effects. Photothermal therapy effectively absorbs the photothermal transducers in the near-infrared region (NIR), which induces the photothermal effect to work. Although PTT has a better role in tumor therapy, it also suffers from low photothermal conversion efficiency, biosafety, and incomplete tumor elimination. Therefore, the use of nanomaterials themselves as photosensitizers, the targeted modification of nanomaterials to improve targeting efficiency, or the combined use of nanomaterials with other therapies can improve the therapeutic effects and reduce side effects. Notably, noble metal nanomaterials have attracted much attention in PTT because they have strong surface plasmon resonance and an effective absorbance light at specific near-infrared wavelengths. Therefore, they can be used as excellent photosensitizers to mediate photothermal conversion and improve its efficiency. This paper provides a comprehensive review of the key role played by noble metal nanomaterials in tumor photothermal therapy. It also describes the major challenges encountered during the implementation of photothermal therapy.

Sonodynamic therapy (SDT) has attracted significant attention in recent years as it is an innovative approach to tumor treatment. It involves the utilization of sound waves or ultrasound (US) to activate acoustic sensitizers, enabling targeted drug release for precise tumor treatment. This review aims to provide a comprehensive overview of SDT, encompassing its underlying principles and therapeutic mechanisms, the applications of nanomaterials, and potential synergies with combination therapies. The review begins by introducing the fundamental principle of SDT and delving into the intricate mechanisms through which it facilitates tumor treatment. A detailed analysis is presented, outlining how SDT effectively destroys tumor cells by modulating drug release mechanisms. Subsequently, this review explores the diverse range of nanomaterials utilized in SDT applications and highlights their specific contributions to enhancing treatment outcomes. Furthermore, the potential to combine SDT with other therapeutic modalities such as photothermal therapy (PTT) and chemotherapy is discussed. These combined approaches aim to synergistically improve therapeutic efficacy while mitigating side effects. In conclusion, SDT emerges as a promising frontier in tumor treatment that offers personalized and effective treatment options with the potential to revolutionize patient care. As research progresses, SDT is poised to play a pivotal role in shaping the future landscape of oncology by providing patients with a broader spectrum of efficacious and tailored treatment options.

Carrier-free nanoparticles (NPs) via chemotherapeutic drug–drug conjugate assembly are a promising alternative for tumor chemotherapy. However, these NPs are still hindered via their nonspecific internalization into certain healthy cells and tissues. Herein, dual-acting methotrexate (MTX) and mannose (MAN) were conjugated via a hydrolyzable ester bond to synthesize a MTX–MAN conjugate as one molecule, which could be directly self-assembled into stimulus-responsive carrier-free NPs (MTX–MAN NPs) in aqueous solution. Such carrier-free MTX–MAN NPs with an accurate drug to sugar ratio could achieve on-demand drug release by dual stimuli of lysosomal acidity and esterase. Besides, MTX–MAN NPs could be dual-recognized by tumor cells in vitro and specifically by tumors in vivo. Moreover, the large proportion of MAN located on the NPs’ surface could exert a shielding effect to avoid phagocytosis of macrophages, leading to long blood circulation. Therefore, the MTX–MAN NPs sharply reduced the drug dosage and decreased the toxicity to normal cells and tissues. Further in vitro and in vivo studies consistently confirmed that the MTX–MAN NPs exhibited superior tumor accumulation and highly synergistic chemotherapeutic effects. Furthermore, we found for the first time that MAN could enhance the antitumor activity of MTX. Considering that bi-functional MTX and MAN are approved via the FDA, and MAN is highly biosafe, the dual-self-recognizing, stimulus-responsive, and carrier-free MTX–MAN NPs might be a simple, selective, and safe chemotherapeutic strategy.

Chemotherapy has been widely applied in oncotherapy. However, the development of multidrug resistance (MDR) has diminished the effectiveness of anticancer drugs against tumor cells. Such resistance often results in tumor recurrence, metastasis, and patient death. Fortunately, nanoparticle-based drug delivery systems provide a promising strategy by codelivery of multiple drugs and MDR reversal agents and the skillful, flexible, smart modification of drug targets. Such systems have demonstrated the ability to bypass the ABC transporter biological efflux mechanisms due to drug resistance. Hence, how to deliver drugs and exert potential antitumor effects have been successfully explored, applied, and developed. Furthermore, to overcome multidrug resistance, nanoparticle-based systems have been developed due to their good therapeutic effect, low side effects, and high tumor metastasis inhibition. In view of this, we systematically discuss the molecular mechanisms and therapeutic strategies of MDR from nanotherapeutics. Finally, we summarize intriguing ideas and future trends for further research in overcoming MDR.

Clinical drug administration aims to deliver drugs efficiently and safely to target tissues, organs, and cells, with the objective of enabling their therapeutic effects. Currently, the main approach to enhance a drug’s effectiveness is ensuring its efficient delivery to the intended site. Due to the fact that there are still various drawbacks of traditional drug delivery methods, such as high toxicity and side effects, insufficient drug specificity, poor targeting, and poor pharmacokinetic performance, nanocarriers have emerged as a promising alternative. Nanocarriers possess significant advantages in drug delivery due to their size tunability and surface modifiability. Moreover, nano-drug delivery systems have demonstrated strong potential in terms of prolonging drug circulation time, improving bioavailability, increasing drug retention at the tumor site, decreasing drug resistance, as well as reducing the undesirable side effects of anticancer drugs. Numerous studies have focused on utilizing polysaccharides as nanodelivery carriers, developing delivery systems based on polysaccharides, or exploiting polysaccharides as tumor-targeting ligands to enhance the precision of nanoparticle delivery. These types of investigations have become commonplace in the academic literature. This review aims to elucidate the preparation methods and principles of polysaccharide gold nanocarriers. It also provides an overview of the factors that affect the loading of polysaccharide gold nanocarriers with different kinds of drugs. Additionally, it outlines the strategies employed by polysaccharide gold nanocarriers to improve the delivery efficiency of various drugs. The objective is to provide a reference for further development of research on polysaccharide gold nanodelivery systems.