Urological cancers, encompassing bladder, upper urinary tract, kidney, prostate, testis, and penile cancers, affected more than 2.5 million individuals in 2020. This number is on the rise globally owing to population growth and aging. Among genitourinary malignancies, bladder, kidney, and prostate cancers stand out as the most frequently diagnosed and are responsible for over 760,000 deaths annually worldwide [1]. Despite optimal treatment approaches with different combinations of surgery, radiation, and systemic therapies, the increasing incidence and mortality rates of urologic cancers highlight the urgent need for better therapeutic management and early diagnosis strategies. Prostate cancer continues to be the leading cause of death in men in 48 countries. Meanwhile, bladder cancer not only ranks as the 9th leading cause of cancer death, but also incurs the highest lifetime treatment costs [1,2]. Local or systemic chemotherapy effectiveness is hindered by low tumor specificity in commonly utilized drugs and poor aqueous solubility of various agents, leading to both local and systemic toxicities [3,4]. Drug efficacy is further limited by drug transportation to and retention in tumor tissue, which depend on drug and formulation properties, vasculature, and type of tumor [5,6]. Urological cancers face additional unique barriers; for example, maintaining a consistent therapeutic dose for bladder cancer is difficult due to urine dilution of drugs.

One way to improving chemotherapy safety and effectiveness is through nanomedicine, which utilizes nanoparticles for imaging, diagnostics, and treatment [7]. Nanocarriers (NCs), a subset of nanoparticles (generally 1–100 nm in size), modulate drugs to enhance their safety, solubility, and bioavailability [8]. NCs can passively or actively target cancerous tissues by altering the chemical properties of known chemotherapeutics, like encapsulating drugs with molecules to change their solubility or surface markers [8]. Passive targeting exploits the enhanced permeability and retention (EPR) effect, allowing NCs to enter and accumulate in tumors due to leaky blood vessels and poor lymphatic drainage [8]. In contrast, active targeting uses specific ligands to direct NCs to cancer cells [8].

Two types of passively targeted NCs have been approved for clinical use: lipid-based NCs and nanoparticle-albumin bound (NAB) [9]. Lipid-based NCs, like liposomes made of phospholipids and glycerides [8], include PEGylated liposomal doxorubicin, which extends doxorubicin's half-life, targets tumors through EPR, and reduces cardio- and gastrointestinal toxicity [10]. NAB encapsulates drugs in albumin to reduce toxicity and improve pharmacokinetics [11], with nab-paclitaxel as a notable example, allowing the suspension of the drug in normal saline rather than the highly toxic but necessary solvent of polyoxyethylated castor oil or ethanol [12]. This has allowed higher doses of paclitaxel in breast cancer with better overall response rates [12].

Despite these successes, skepticism towards the use of NCs is growing [7,13,14] due to promising pre-clinical data often not translating to human efficacy, suggesting poor animal models for EPR [13,14]. NCs may confer improved safety profiles but not necessarily increased efficacy, as seen by PEGylated liposomal doxorubicin with reduced cardiotoxicity but equal efficacy [10].

Nevertheless, active research continues, with clinical trials involving bladder, prostate, and kidney cancers. These trials largely center around 3 broad types of NCs: lipid-based, NAB, and polymeric (Fig. 1). Polymeric NCs, a newer and broader category, carry drugs by encapsulating or adsorbing them onto diverse polymer networks [15]. The objective of this review is to assess the safety and efficacy outcomes of NCs in the treatment of urologic cancers. We also offer insights into progress and clinical utility for novel NC technologies in this setting.