Contemporary imaging like MRI and CT has already improved our ability to detect anatomical and oncologic abnormalities. However, there are still limitations restricting the sensitivity and specificity of our modern technology [5]. Nanoparticles provide an interesting solution by utilizing high surface area; these nanoparticles allow extensive space for attachment of imaging agents and tumor-targeted ligands. Likewise, due to their specific size, nanoparticles undergo a process called enhanced permeability and retention (EPR) allowing them to escape renal clearance, while being small enough to extravasate and concentrate in the leaky vascular and lymphatic drains of developing tumors [3].

The first landmark paper on urological imaging was published in 2003. Dr. Harinsghani’s group at Massachusetts General Hospital demonstrated the use of superparamagnetic nanoparticles in detection of occult metastatic prostate cancer. In a study of 80 prostate cancer patients of whom 33 had positive lymph nodes the authors reported that superparamagnetic particles via MRI were able to identify 100% of those patients preoperatively. This improvement was compared to a 45.4% detection based on standard MRI size criteria. By gaining access to interstitial lymphatic fluid these particles were able to enhance high-resolution MRI to detect clinically occult lymph node metastasis [6]. Feldman et al. applied the same technology in the lymph node metastasis detection in prostate, bladder, penile, and testicular cancers and found significant improvements in the sensitivity, specificity, and accuracy compared to conventional imaging [7].

As nanoparticle innovation continues to improve, further investigation has achieved targeted imaging enhancement. Recently, Mirzaei et al. has synthesized a nanodendrimer conjugated with a monoclonal antibody against prostate cancer and further chelating the particle with the imaging contrast agent, gadolinium. The group’s early research with a complex nanoprobes demonstrates the capability to develop highly sensitive, specific, and targeted imaging augmentations [8].

Another promising vector for nanotechnology in imaging is the exploration of quantum dots. These are nano sized fluorescence-based optical probes with long half-lives, strong luminescence, and narrow emission range which can be tuned to near infrared light, allowing unmatched sensitivity in deeper penetrating [9]. Several in vivo and in vitro trials have shown potential for quantum dots. However, debate exists about the relative toxicity and low clearance of these particles [3]. Researchers like Ma et al. have developed potential solutions. The authors created a novel chitosan coated quantum dot that has increased sensitivity to zinc, a compound found in high concentrations in prostate cancer, while the coating also reduces any potential toxicity leak [10]. Quantum dots continue to provide promise in the diagnosis of urologic cancers.

Gene therapy has been a heavily researched field due to the promise of overcoming genetic illness with the introduction or ectopic expression of healthy genes. Nanoparticles have been implemented as non-viral vectors as a result of good biocompatibility, unlimited DNA carrying capacity, and specific cell targeting [11]. Early research has focused on cationic lipids such as liposomes in the delivery of genes. Larchian and his group from The Cleveland Clinic, in 2000, developed a liposome-mediated immune gene therapy using interleukin-2 and B71 in a murine bladder cancer model. The authors found that their regiment significantly improved tumor-free survival and was a safer and more effective compared to retroviral systems [12]. Other researchers like Hattori and Maitani developed nanoparticles with the addition of novel folate-link ligands for more specific delivery to prostate cancer. Their research was the first to selectively deliver DNA to prostate cancer in vitro that then enhanced gene expression [13]. Moffatt et al. from MD Anderson Cancer Center as well as Mukherjee from Johns Hopkins have been able to pair nanoparticles with prostate specific membrane antigen (PSMA) [14, 15]. Moffatt et al. using a targeted DNA molecular vector was also able to demonstrate a 20-fold increase in gene delivery over control in a mouse model [14]. These early studies illustrate the ability to create effective non-viral gene carriers while also improving uptake via surface markers and specific ligands.

Nanotechnology as a vector for drug delivery is perhaps the most studied platform for this new technology. Nanoparticles can effectively package drugs and thereby protect them from the in vivo microenvironment while also decreasing and minimizing systematic toxicity. Likewise, particles can be tagged with targeted ligands and markers and due to the EPR effect; particles have increased drug half-life, circulation, and enhanced bioavailability [16]. The earliest milestone for nanotechnology in drug delivery was the FDA approval of Doxil , a liposomal-based doxorubicin formulation, in 1995. This decision opened the floodgates for research to encapsulate other drugs for nanoparticle delivery [17].

In 1994 Okada et al. successfully loaded PLGA particles with leuprorelin for the treatment of prostate cancer. The group was able to use the stability of PLGA particles to create a 3-month depot injectable with linearly sustained drug release over 13 weeks [18]. Other groups like Sahoo et al. were also able to formulate paclitaxel-loaded PLGA particle with the addition of transferrin conjugation thereby selectively targeting prostate cancer. The authors were able to show in a murine prostate model that particles with transferrin and paclitaxel selectively killed tumor greater than drug or drug and particle alone [19].

In a phase II clinical trial of 34 patients with unresectable transitional cell carcinoma Winquist et al. investigated an IV pegylated-liposomal doxorubicin . The authors showed that six patients had partial response while seven had stable disease. Likewise, the authors noticed no clinical cardiotoxicity in the cohort, a typical dose-limiting factor in free drug regiments. Therefore, the authors demonstrated that nanoparticle formulations could alter toxicity profiles and improve response rate [20].

In the treatment of renal cell carcinoma (RCC) Sumitomo et al. in 2008 explored the use of an SN38 releasing nanodevice in disease progression. The authors found the nanoparticle was able to significantly decrease the number of pulmonary metastasis in a murine model versus control or drug alone [21]. In 2014 Liu et al. from Tulane University was able to successfully encapsulate the tyrosine kinase inhibitor Sorafenib one of the front line medications for the treatment of RCC, demonstrating that the class of tyrosine kinase inhibitor drugs and their hydrophobic interactions could be overcome [22].

Nanotechnology is also being used in the treatment of bladder cancer. Early research by Kiyokawa et al. in 1999 showed that injected liposomal doxorubicin in canines demonstrated 15–100 times greater concentration in regional lymph nodes and 70–930 times greater in whole bladder wall [23]. Lu et al. showed similar improvements with their formulation of paclitaxel loaded gelatin nanoparticles. The authors showed a 2.6 times greater concentration of drug dose in canine bladder model versus commercial free drug formulation while also demonstrating rapidly releasing drug with good cell kill [24]. Research in drug delivery has also branched out to incorporate other forms of nanoparticles. The group Chen et al. was able to develop a pirarubicin-loaded carbon nanotube . The authors found significant tumor depression both in vitro and in a rat bladder cancer model compared to drug alone. Interestingly the authors also noted that in contrast to free drug groups the rats treated with nanoparticles did not exhibit any significant side effects and no changes to both hepatic and renal function [25].

Finally, McKiernan from Columbia University demonstrated in a Phase II trial of intravesical nanoparticle albumin bound paclitaxel, an increased response rate of 35.7% in treatment of nonmuscle invasive bladder cancer following bacillus Calmette-Guerin treatment failure. The intravesicle nanoparticle paclitaxel had minimal toxicity with complete response rate remaining durable at 1 year follow-up [26].

Thermal ablation to treat urological maladies has significant clinical precedent. High intensity focused ultrasound, cryotherapy, and radiofrequency ablation are surgical ablation modalities used worldwide. Combination of thermal treatment with nanocarriers is an interesting new concept that allows synergistic targeted effect while sparing unaffected tissue [3]. Stern et al. from University of Texas Southwestern Medical Center explored gold nanoshells in the ablation of prostate cancer cells in vitro. The group found that laser combined with nanoshells could eradicate all cells, while laser or shells alone had no influence on viability [27]. The same group applied their platform to a mouse model and showed a 93% tumor necrosis and regression after harvest in the treatment arm. Likewise, when paired the laser and gold had a mean temperature change of 28.9 versus 13.8 °C in just laser and saline [28]. In a similar animal study done by Lee et al. a dual gold nanorod and tyrosine kinase inhibitor albumin particle was formulated. The authors reported that when activated by laser there was synergistic response in both thermal ablation and drug release that could more effectively eradicate tumor [29].

Another model commonly used in ablation is magnetic iron oxide. Kawai et al. used magnetic cationic liposomes to ablate prostate cancer in a mouse model using an alternating magnetic field. The authors were able to reach core tumor temperatures of 45 °C with negligible body temperature change in the rest of the mouse. Likewise, measuring heat shock proteins, they found a significant immune response along with noticeable cellular necrosis [30]. The exploration of magnetic hyperthermia will be an interesting platform for nanotechnology since it can successfully ablate tumors based on image guidance, in addition, avoids the potential of skin burns experienced with some of the ablation modalities [31].

Carbon nanotubes , first discovered in 1991 by physicist Sumio Iijima, have also been heavily studied in thermal ablation [3]. Fisher et al. demonstrated in both murine renal cancer and in vitro prostate cancer cell lines that multi wall carbon nanotubes (MWCNT) incubated in cell lines and activated with 5 min of laser could lead to temperature increase of 43 °C and 100% cell death [32]. Likewise the group Burke et al. used MWCNT in the ablation of RCC in nude mice. Despite using short treatment times with low laser settings the authors were able to achieve greater than 3.5-month remission in 80% of the mice treated [33].