Table 3. Effect of exosome production and internalization on PTX accumulation and cytotoxicity in cells: Model-simulated results.

Simulations were performed for Donor cells treated with 1 or 1000 nM PTX for 24 h. The resulting values of C_cell,total, C_cell,tubulin and Cytotoxicity (E, rate constant of drug-induced cell death) are represented as area-under-curve from 0 to 24 h. E was calculated as $k_{\mathit{kill}}\cdot \left(\frac{{C_{\mathit{cell},\mathit{tubulin}}}^n}{{C_{\mathit{cell},\mathit{tubulin}}}^n+I{C}_{50}^n}\right)$. The original values of model parameters are 31 h⁻¹ for k_sort,exo, 0.105 h⁻¹ for k_rel,exo, 0.038 pmole·h⁻¹·cell⁻¹ for Jmax_inter,exo, and 59.2 μM for B_{tubulin,initial}. With the exception of B_{tubulin,initial} where the low and high values were one-half or 2-times the original values, the low and high values of all other parameters were one-tenth or 10-times the original values. Signs in the table correspond to minimal change of <20% (−), increase or decrease of 20–50% (↑ and ↓), 51–100% (↑↑ and ↓↓), 101–200% (↑↑↑ and ↓↓↓), and >200% (↑↑↑↑ and ↓↓↓↓).

Parameter				A. Effects on Donor cells						B. Effects on Recipient cells
				1 nM			1000 nM			1 nM			1000 nM
Ccell,total	Ccell,tubulin	E	Ccell,total	Ccell,tubulin	E	Ccell,total	Ccell,tubulin	E	Ccell,total	Ccell,tubulin	E
Exosome production	ksort,exo	Low	–	–	–	↑	–	–	↓	↓	↓↓	↓	↓	↓↓
		High	–	–	–	↓	–	–	↑	↑	↑↑	↑↑	↑↑	↑↑
	krel,exo	Low	↑	↑↑	↑↑ ↑↑	↑	↑	–	↓	↓	↓↓	↓↓	↓↓	↓↓↓
		High	↓	↓↓	↓↓ ↓↓	↓	↓	–	↑↑	↑↑	↑↑ ↑	↑↑	↑↑	↑↑↑ ↑
Exosome internalization	Jmaxinter,exo	Low	–	↓	↓	–	–	–	↑	↑	↑↑ ↑	↑↑	↑↑	↑↑↑ ↑
		High	–	↑	↑	–	–	–	↓	↓	↓	↓	↓	↓↓
Tubulin binding capacity	Btubulin,initial	Low	↓	↓↓	↓↓ ↓	↓↓	↓↓↓	–	↑	↑	↑	↑	↑↑	↑↑
		High	↑	↑↑	↑↑ ↑	↑↑	↑↑↑	–	↓	↓	↓↓	↓	↓	↓↓