Progress of Cancer Nanotechnology as Diagnostics, Therapeutics, and Theranostics Nanomedicine: Preclinical Promise and Translational Challenges

Abstract

Early detection, right therapeutic intervention, and simultaneous effectiveness mapping are considered the critical factors in successful cancer therapy. Nevertheless, these factors experience the limitations of conventional cancer diagnostics and therapeutics delivery approaches. Along with providing the targeted therapeutics delivery, advances in nanomedicines have allowed the combination of therapy and diagnostics in a single system (called cancer theranostics). This paper discusses the progress in the pre-clinical and clinical development of therapeutics, diagnostics, and theranostics cancer nanomedicines. It has been well evident that compared to the overabundance of works that claimed success in pre-clinical studies, merely 15 and around 75 cancer nanomedicines are approved, and currently under clinical trials, respectively. Thus, we also brief the critical bottlenecks in the successful clinical translation of cancer nanomedicines.

Keywords: and targeted cancer chemotherapy; cancer nanomedicines; diagnostics; metallic nanoparticles; theranostics.

Figure 1

(A) Different types of nanomedicine utilized in cancer diagnosis and therapy; (B) various physicochemical characteristics of nanomedicine influencing its biopharmaceutical performance.

Figure 2

Illustration depicts the utilization of cancer nanomedicine in photothermal therapy (PTT) and photodynamic therapy (PDT) leads to cancer cell death.

Figure 3

Illustration depicts in vivo evaluation of near-infrared fluorescent dye-loaded liposomal nanomedicine as cancer diagnostics for the image-guided nuclear delivery of the encapsulated dye (A) in vivo imaging of delivery of NIR-fluorescence dye (DY676-COOH) in mice bearing FAP-expressing fibrosarcoma HT1080-hFAP [1] and FAP-expressing human melanoma MDA-MB435S [2] after i.v. injection for 0–48 h. (B) Semiquantitative analysis of fluorescence intensities of a region of interest on respective tumors or background (thigh region) at a given time point. (C) Photograph and NIR-fluorescence images of tumor tissue excised after the 48 h of liposomal nanomedicine (monospecific and bispecific) administration indicating intense liposomal fluorescence in case of mice bearing FAP-expressing fibrosarcoma HT1080-hFAP. Reproduced from [94], MDPI, 2020. Note: Three groups of tumor-bearing mice were treated with two types of monospecific liposome (HER2-IL and FAP-IL) and one Bispecific liposome (Bi-FAP/HER2-IL). * significant compared to control, ** highly significant compared to control.

Figure 4

Illustration depicts diagnostic/imaging agent and therapeutic agent consist in a single NPs system as cancer theranostics.

Figure 5

Illustration depicts the formulation design, in vitro and in vivo evaluation of folate-modified raltitrexed-loaded multifunctional nanoparticles (RTX/FA NP) as cancer theranostics. (i) Physical characterization of raltitrexed (RTX) and RTX/FA NP formulations; [A] TEM images, [B] mean size and zeta-potential, [C] intensity-derived size distribution, [D] IR spectra. (ii) Cell viability assay of CT26 cancer cells after 72 h treatment. (iii) In vitro cellular uptake of developed nanomedicine through fluorescence microscopy. (iv) Biodistribution of NP formulations injected into mice bearing CT26 tumors; [A] comparative profile of mean relative flux in various organ from different treatment group, [B] comparative profile of signal intensity of tumors from different treatment group, [C] comparative profile of mean average radiance of tumors from the different treatment group. Reproduced from [129], MDPI, 2020. * significant compared to control.

Figure 6

Illustration depicts worldwide nanomedicine market revenue in terms of different therapeutics areas (source; based on market data forecast and Infoholics Report December 2017).