Industrialization's eye view on theranostic nanomedicine

Abstract

The emergence of nanomedicines (NMs) in the healthcare industry will bring about groundbreaking improvements to the current therapeutic and diagnostic scenario. However, only a few NMs have been developed into clinical applications due to a lack of regulatory experience with them. In this article, we introduce the types of NM that have the potential for clinical translation, including theranostics, multistep NMs, multitherapy NMs, and nanoclusters. We then present the clinical translational challenges associated with NM from the pharmaceutical industry's perspective, such as NMs' intrinsic physiochemical properties, safety, scale-up, lack of regulatory experience and standard characterization methods, and cost-effectiveness compared with their traditional counterparts. Overall, NMs face a difficult task to overcome these challenges for their transition from bench to clinical use.

Keywords: ISO and ASTM international; drug nanoformulation; investigational new drug (IND); multifunctional nanotheranostics; multistep nanotheranostics; theranostics; translational nanomedicine.

FIGURE 1

(A) Design and application of PFP-m-Fe3O4@PGTTC, (B) temperatures of the tumor tissue at various time points, (C) photographs of H22-tumor-bearing mice with various treatments. (D) Comparison of subcutaneous tumor volume changes among groups, (E) comparison of subcutaneous body weight changes among groups, (F) survival curves of mice within 60 days, (G) representative H&E-, Ki-67-, and CD31-stained images of tumor slices collected from mice in various groups, and (H) H&E-stained images of the major organs (heart, liver, spleen, lung, and kidney) from various groups. ****p < 0.0001, ***p < 0.001, and **p < 0.01. Reproduced with permission (Lu et al., 2021). Copyright 2021, American Chemical Society.

FIGURE 2

(A) Schematic representation of AuPt@CuS NSs for enhanced synergistic radio-photothermal therapy, (B) weights of dissected tumors from each group, (C) relative tumor volumes after various treatments (n = 4), (D) digital photographs of the dissected tumors, (E) photographs of mice after treatment. (F,G) H&E-stained images of tumor sections following treatment. Reproduced with permission (Cai et al., 2021). Copyright 2021, American Chemical Society.

FIGURE 3

(A) Schematic illustration of the formulation of the NPs, release of TG-S in the TME, penetration of tumor tissue, and cellular uptake. (B–E) Fluorescent images of A549 tumor spheroids incubated with saporin (B), TG-S (C), and TG-S NPs at pH 7.4 (D) or 6.5 (E) for 2, 4, or 8 h, as measured by CLSM. The saporin protein was conjugated to Cy5.5 for fluorescence imaging. (F,G) Fluorescence images of A549 tumor spheroids incubated with FAM-labeled TG-S (green) and Cy5.5-labeled TG-S NPs (red) at pH 7.4 (F) or 6.5 (G) for 2 h, as measured by CLSM. Scale bar, 500 μm. Reproduced with permission (Fu et al., 2022). Copyright 2022, American Chemical Society.

FIGURE 4

(A) In vivo SWIR imaging (reverse contrast) of WT 129/Ola mouse vasculature before imaging processing (raw) and after MC restoration (MCR) and an additional filtering (MCR + HP filter). (B) MCR + HP filter-treated SWIR images (false colors) (i) 1.5 s, (ii) 5 s, (iii) 25 s, and (iv) 65 s after intravenous injection of an AuMHA/TDT bolus (360 μm; 200 μl). Reproduced with permission (Yu et al., 2020). Copyright 2020, American Chemical Society.

FIGURE 5

(A) Scheme of siRNA treatment. Panc-1-luc cells were injected into the pancreas head of Balb/c nude mice to form orthotopic tumors. After 2 weeks, mice were divided into different groups. Mice received various formulations via tail-veil injections, six times, and were euthanized on day 28. (B) Changes in mouse body weight during treatments. (C) In vivo whole-body bioluminescence images of mice on day 14 and day 28, which indicated the tumor size before and after siRNA treatment. Bioluminescence signals resulted from the interaction of luciferase from Panc-1-luc cells with D-luciferin injected into the mice before imaging. (D) Ex vivo bioluminescence images of orthotopic pancreatic tumors and tumor metastases into mesenteries on day 28. Yellow lines indicate the locations of primary tumors in the pancreas. Scale bar, 1 cm. (E) Tumor images on day 28. Scale bar, 5 mm. (F) Quantification of in vivo bioluminescence to evaluate the primary tumors in mice on day 28. (G) Quantification of tumor metastases by the sum of ex vivo bioluminescence detected in the mesenteries on day 28. (H) Weight of the isolated tumors. (I) NGF mRNA and (J) NGF protein expression levels in orthotopic tumors. Reproduced with permission (Lei et al., 2017). Copyright 2017, Springer Nature.